Chemical processing microsystems comprising high-temperature parallel flow microreactors

ABSTRACT

A chemical processing microsystem useful for identifying and optimizing materials (e.g., catalysts) that enhance chemical processes or for characterizing and/or optimizing chemical processes is disclosed. The chemical processing microsystem comprises a plurality of microreactors  600  and, in a preferred embodiment, a plurality of microseparators  900  integral with the chemical processing microsystem  10.  The microreactors  600  are preferably diffusion-mixed microreactors formed in a plurality of laminae that include a modular, interchangeable candidate-material array  100.  The material array  100  comprises a plurality of different candidate materials (e.g., catalysts), preferably arranged at separate, individually addressable portions of a substrate (e.g., wafer). The microseparators  900  are similarly formed in a plurality of laminae that include a modular, interchangeable adsorbent array  700.  The adsorbent array  700  comprises one or more adsorbents, preferably arranged at separate, individually addressable portions of a substrate to spatially correspond to the plurality of different candidate materials. Modular microfluidic distribution systems are also disclosed. The chemical processing microsystem can be integrated into a material evaluation system that enables a comprehensive combinatorial material science research program.

This application claims priority to commonly owned, co-pending U.S.patent application Ser. No. 60/122,704 filed Mar. 3, 1999 entitled“Chemical Processing Microsystems, Diffusion-Mixed Microreactors andMethods for Preparing and Using Same”, which is hereby incorporated byreference for all purposes.

BACKGROUND OF THE INVENTION

The present invention relates generally to the field of combinatorialchemistry and, in preferred applications, to the field of combinatorialmaterials science. In particular, the invention relates to systems andmethods employing microfluidic devices in chemical processes, forcharacterizing and optimizing such chemical processes and foridentifying materials that enhance such chemical processes. Preferredembodiments of the invention relate to microchemical processing systems,to diffusion-mixed microreactors, and to methods for identifying oroptimizing heterogeneous catalysts.

Combinatorial chemistry refers generally to methods for synthesizing acollection of chemically diverse materials and to methods for rapidlytesting or screening this collection of materials for desirableperformance characteristics and properties. Combinatorial chemistryapproaches have greatly improved the efficiency of discovery of usefulmaterials. For example, material scientists have developed and appliedcombinatorial chemistry approaches to discover a variety of novelmaterials, including for example, high temperature superconductors,magnetoresistors, phosphors and catalysts. See, for example, U.S. Pat.No. 5,776,359 to Schultz et al. In comparison to traditional materialsscience research, combinatorial materials research can effectivelyevaluate much larger numbers of diverse compounds in a much shorterperiod of time. Although such high-throughput synthesis and screeningmethodologies are conceptually promising, substantial technicalchallenges exist for application thereof to specific research andcommercial goals.

Microfluidics refers generally to the field of miniaturized fluidicsystems. Microfluidic systems have been designed to perform similartasks as larger scale commercial fluid systems, and have included anumber of different microcomponents such as fluid-distribution channels,valves, pumps, motors, mixers, heat-exchangers, condensers, evaporators,chemical reactors, chemical separators, sensors and actuators, amongothers. When microfluidic systems are integrated with microelectronics,the integrated systems are typically referred to asmicroelectromechanical systems (MEMS). When microfluidic systems includea chemical reactor and/or a chemical separator, the systems can bereferred to as chemical processing Microsystems. Microfluidic systemshave typically been fabricated using technology known in connection withintegrated circuit fabrication.

A number of chemical processing Microsystems have been developed toeffect chemical and/or biochemical conversions, alone or in combinationwith other unit operations such as separation and analysis. See, forexample, Ehrfeld et al., Potentials and Realizations of Microreactors,DECHEMA Monographs Vol. 132, pp. 1-28 (1995) and references citedtherein. A microreactor is a common component of such chemicalprocessing Microsystems, and a number of different microreactor designshave been developed to date. One type of microreactor design includesmicrochannels in which a reaction occurs as a fluid moves through one ormore relatively long channels of relatively small hydraulic diameter.Microchannels offer a large surface area to volume ratio and, whencoupled with microscale heat exchangers, offer exceptional temperaturecontrol for exothermic or endothermic reactions. Exemplary channel-typemicroreactors are disclosed in U.S. Pat. No. 5,811,062 to Wegeng et al.,U.S. Pat. No. 5,534,328 to Ashmead et al., U.S. Pat. No. 5,690,763 toAshmead et al., Tonkovich et al., The Catalytic Partial Oxidation ofMethane in a Microchemical Reactor, AIChE 2^(nd) InternationalConference on Microreaction Technology, pp. 45-53 (1998), Honicke etal., Heterogeneously Catalyzed Reactions in a Microreactor, DECHEMAMonographs Vol. 132, pp. 93-107 (1995), and van den Berg et al., ModularConcept for Miniature Chemical Systems, DECHEMA Monographs Vol. 132, pp.109-123 (1995). Cell-type microreactors, in which a reaction occurswhile a fluid resides in a cell, have likewise been employed. Exemplarycell-type microreactors are disclosed in U.S. Pat. No. 5,843,385 toDugan, U.S. Pat. No. 6,603,351 to Cherukuri et al., PCT Application WO98/07206 of Windhab et al., and van den Berg et al., Modular Concept forMiniature Chemical Systems, supra. Microreactors that provide passivemixing and reaction of reactants in “Y”-shaped or “T”-shapedmicrochannels are disclosed in Burns et al., Development of aMicroreactor for Chemical Production, AIChE 2^(nd) InternationalConference on Microreaction Technology, pp. 39-44 (1998), and inSrinivasan et al., Micromachined Reactors for Catalytic PartialOxidation Reactions, AIChE Journal, Vol. 43, No. 11, pp.3059-3069(1997). Microreactors for heterogenous phase reactions, such asgas-liquid or gas-solid reactions, are reported in Lowe et al.,Microreactor Concepts for Heterogeneous Gas Phase Reactions, AIChE2^(nd) International Conference on Microreaction Technology, pp. 63-73(1998). Reactors specifically designed for certain classes of reactions,such as electrochemical reactions or photo-induced reactions havelikewise been contemplated. See, for example, Matlosz et al.,Microsectioned Electrochemical Reactors for Selective Partial Oxidation,AIChE 2^(nd) International Conference on Microreaction Technology, pp.54-59 (1998).

Contemplated applications for such chemical processing microsystemsinclude end-use production of hazardous chemicals, processcharacterization and optimization, and combinatorial chemistry. Whilecombinatorial chemistry applications have been contemplated, the variouschemical microreactor designs reported to date, however, have not beenincorporated into systems suitable for large-scale, or evenmoderate-scale, combinatorial chemistry research, and particularly, forcombinatorial material science research directed to heterogeneouscatalyst screening for identification and/or optimization. For example,although parallel-type reactors and microreactors have been reported(see, e.g.,.U.S. Pat. No. 3,431,077 to Danforth, U.S. Pat. No. 4,099,923to Milberger, U.S. Pat. No. 5,603,351 to Cherukuri et al. and PCTApplication WO 98/07206 of Windhab et al.), none of these reactors aresatisfactory for combinatorial materials science applications. These andother microreactor designs known in the art do not address importantconcerns such as the loading, and/or unloading of larger numbers ofcandidate materials (e.g., catalysts) for screening, the supplying ofreactants to a plurality of microreactors, the controlling of thereaction conditions in a plurality of microreactors, and/or theevaluating of candidate materials for specific properties of interest(e.g., catalytic activity). Known microreactors also have commonlimitations, for example, with respect to a low throughput (e.g., thenumber of catalysts that can be screened over a given period of time), anarrow distribution of heterogeneous catalyst contact times, a largeamount of each (often expensive) candidate catalyst required to effectthe chemical conversion, the potential inherent negative influence ofmicroreactor materials on a reaction of interest, a high degree ofcomplexity, a lack of flexibility for analyzing the results of thechemical conversion, and, in some cases, a lack of scalability ofresearch results to production-scale systems.

The present invention, as described in detail below, overcomes many, ifnot all of such shortcomings.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to providecost-effective approaches for high-throughput combinatorial chemistryresearch and development, including particularly, research directed tothe identification and optimization of new materials that enhance achemical process and research directed to chemical processcharacterization and optimization.

It is also an object of the invention to provide chemical processingMicrosystems that are relatively inexpensive to manufacture and use,that are flexible as to applications and variations, and that provideresults which are scaleable to commercially significant systems.

Briefly, therefore, the present invention is directed to a chemicalprocessing microsystem. The chemical processing microsystem generallycomprises four or more microreactors and a fluid distribution system.Each of the microreactors comprise a surface defining a reaction cavityfor carrying out a chemical reaction, an inlet port in fluidcommunication with the reaction cavity, and an outlet port in fluidcommunication with the reaction cavity. The reaction cavity has a volumeof not more than about 10 ml, and in some applications, not more thanabout 3 ml, 1 ml, 100 μl, 10 μl or 1 μl. The fluid distribution systemcan supply one or more reactants from one or more external reactantsources to the inlet port of each reaction cavity and can discharge areactor effluent from the outlet port of each reaction cavity to one ormore external effluent sinks.

In one embodiment, the four or more microreactors of the chemicalprocessing microsystem are arranged in a substantially planar array witha planar density of not less than about 1 microreactors/cm² andpreferably not less than about 5 microreactors/cm².

In another embodiment, the chemical processing microsystem comprisestwo-hundred-fifty or more microreactors.

In a further embodiment, the chemical processing microsystem comprisesten or more microreactors and the distribution system includes amanifold comprising one or more common ports adaptable for fluidcommunication with one or more external reactant sources or one or moreexternal reactor effluent sinks, ten or more terminal ports adaptablefor fluid delivery to or fluid recovery from the ten or moremicroreactors, and a distribution channel providing fluid communicationbetween the one or more common ports and each of the ten or moreterminal ports. The ratio of the number of terminal ports to the numberof common ports is at least about 10:1, and for some applications, atleast about 100:1.

In an additional embodiment, the fluid distribution system of thechemical processing microsystem includes a manifold that comprises acommon port adaptable for fluid communication with one or more externalreactant sources or one or more external effluent sinks, 2^(n) terminalports adaptable for fluid delivery to or fluid recovery from 2^(n)microreactors, and a distribution channel providing fluid communicationbetween the common port and each of the 2^(n) terminal ports, where n isan integer of not less than 2, preferably of not less than 3, and morepreferably of not less than 6. The distribution channel comprises2^(n)-1 channel sections, preferably linear channel sections, connectedwith each other through 2^(n)-1 binary junctions. Each of the 2^(n)-1channel sections has at least three access ports serving as the commonport, as a connection port for a binary junction, or as a terminal port.The microreactors are preferably arranged in a substantially planararray with a planar density of at least 1 microreactor/cm², andpreferably of at least 5 microreactors/cm².

In a still further embodiment, the reaction cavity of each of the atleast four microreactors has a geometry defined by ratios of distancesX, Y, and Z measured within the reaction cavity along three mutuallyorthogonal lines having a common point of intersection at a midpoint ofthe longest line, Z, and oriented with the longest line, Z, normal to atleast one surface that it intersects, and preferably normal to at leasttwo surfaces that it intersects. The ratios of X:Z and Y:Z each rangefrom about 1:2 to about 1:1.

In an alternative embodiment, the chemical processing microsystemfurther comprises four or more microseparators. Each of themicroseparators comprises a surface defining a separation cavity forseparating at least one component of a reactor effluent, an inlet portin fluid communication with the outlet port of one of the microreactorsfor receiving the reactor effluent therefrom, and an outlet port influid communication with the separation cavity for discharging theseparated effluent therefrom. A fluid discharge system can discharge theseparated reactor effluent from the outlet port of each separationcavity to one or more external effluent sinks. The microseparators can,in one exemplary embodiment, further comprise an adsorbent material forseparating, preferably selectively, one or more components of a reactoreffluent stream. The adsorbent material can be accessible for loadingand unloading thereof into and out of the microseparators. For example,the microseparators can be formed in a plurality of adjacent laminaewith at least one of the laminae being an adsorbent-containing laminatecomprising a substrate and one or more adsorbent materials for adsorbingat least one component of the reactor effluent. A releasable seal can besituated between the adsorbent-containing laminate and one or moreadjacent laminae in which the microseparators are formed.

In yet another embodiment, the chemical processing microsystem furthercomprises at least four different candidate materials being investigatedfor properties that enhance a chemical process of interest. Potentialcatalysts are exemplary candidate materials. The candidate materials areindividually resident in the reaction cavity of separate microreactors.Each of the candidate materials comprises, or consists essentially of,an element, compound or composition selected from the group consistingof inorganic materials, metal-ligands and non-biological organicmaterials. The amount of the candidate material in each of thecandidate-material containing microreactors is not more than about 10mg, and for some applications, not more than about 5 mg, or not morethan about 1 mg. The number of microreactors preferably ranges fromabout 7 to about 100, and in some applications from about 100 to about250, from about 250 to about 400, from about 400 to about 1000. Thenumber of microreactors can also be greater than about 1000. Not all ofthe microreactors have to contain a candidate material; rather somemicroreactors can be left as blanks or can contain control materials.Typically, different candidate materials are individually resident inthe separate reaction cavities of at least 2%-100% of the microreactors,preferably of at least about 5% to about 99% of the microreactors. Ananalytical detection system can be in fluid communication with theoutlet port of one or more of the microreactors. The microreactors ofthis embodiment can be further characterized by the various features orcombinations of features summarized in the aforementioned paragraphs.

Each of the candidate-material-containing microreactors in theaforementioned chemical processing microsystem is, in one embodiment,accessible for unloading the candidate materials after the chemicalreaction, and optionally, for reloading a second set of candidatematerials. For example, the microreactors can be formed in a pluralityof adjacent laminae, with at least one of the laminae being a candidatematerial-containing laminate comprising a substrate and the at leastfour candidate materials at separate portions of the substrate. Foraccess, a releasable seal is situated between the material-containinglaminate and one or more adjacent laminae in which the microreactors areformed.

In another embodiment, each of the candidate-material-containingmicroreactors in the aforementioned chemical processing microsystem isformed in a plurality of adjacent laminae. At least one of the laminaecan be a candidate material-containing laminate that comprises asubstrate and the at least four candidate materials at separate portionsof the substrate, but that has an essential absence of fluiddistribution microcomponents (or generally, components), and preferablyalso of temperature-control microcomponents (or generally, components)or other microcomponents (or generally, components). Thematerial-containing laminate can be anodically bonded with adjacentlaminate or can be releasably sealed therewith. Graphite gaskets arepreferred in connection with the releasably sealed embodiment.

The present invention is also directed to methods for preparing achemical processing microsystem for identifying and characterizingmaterials that enhance a chemical reaction. According to such methods,at least four different candidate materials are loaded into four or moremicroreactors such that the candidate materials are individuallyresident in a reaction cavity of a separate microreactor. Each of thecandidate materials are an inorganic material, a metal-ligand, anon-biological organic material or a composition comprising variouscombinations thereof. Each of the microreactors comprise a surfacedefining a reaction cavity having a volume of not more than about 10 μl,an inlet port, and an outlet port as described above. The candidatematerials can be loaded simultaneously, or alternatively, sequentially,into the four or more microreactors. The four or more microreactors canbe formed in a plurality of laminae as described above, with the atleast four candidate materials loaded into the four or moremicroreactors as a material-containing laminate as described above.

The present invention is further directed to methods for identifying oroptimizing catalysts for a chemical reaction of interest. According tothese methods, at least four different candidate materials are loadedinto four or more microreactors of a chemical processing microsystemsuch that the at least four different candidate materials areindividually resident in separate microreactors. Each of themicroreactors comprise a surface defining a reaction cavity having avolume of not more than about 1 ml, preferably less than about 100 μl,or even less than about 10 μl. Each of the candidate materials areelements, compounds or compositions comprising one or more inorganicmaterials, one or more metal-ligands or one or more non-biologicalorganic materials, separately or in various possible combinations.

For such methods, the candidate materials can be loaded simultaneously,or alternatively sequentially, into the four or more microreactors. Inpreferred approaches, the candidate materials are loaded withoutaffecting the structural integrity of a fluid distribution systemthrough which the one or more reactants are supplied to themicroreactors or through which one or more reactor effluents aredischarged from the microreactors.

In such methods, one or more reactants are simultaneously supplied toeach of the at least four candidate material-containing microreactors,and simultaneously contacted with each of the at least four candidatematerials. The reaction conditions are controlled to be conducive to, orintended to be conducive to, effecting the chemical reaction ofinterest. In some approaches, the reaction conditions are controlled tobe substantially the same in each of the four or more microreactors, orat least in some subset of at least four or more microreactors. For manyapplications, the temperature is controlled to be not less than about100° C. and to be substantially the same in each of the four or moremicroreactors or in a subset thereof. For many applications, theresidence time can be controlled to range from about 1 μsec about 1 hourand to be substantially the same in each of the four or moremicroreactors or in a subset thereof. In some applications, the reactionconditions can be controlled such that the reactant residence time,τ_(res,) is longer than the diffusion period, τ_(diff), for the reactioncavity. A reactor effluent is simultaneously discharged from each of theat least four candidate material-containing microreactors.

The at least four candidate materials can, according to such methods, beevaluated for catalytic activity (e.g., yield, conversion) orselectivity for the chemical reaction of interest. The candidatematerials can, for example, be evaluated for catalytic activity by insitu analytical measurement, or analytical measurement of the reactoreffluent. The candidate materials can be evaluated for catalyticactivity by serial, parallel or serial-parallel (subgroup hybrid)analytical measurement. Detection approaches can include, with orwithout pre-separation of analyte component, gas chromatography, massspectroscopy and optical spectroscopy, among other approaches. In apreferred approach, separation of one or more reactor effluentcomponents is effected by adsorbing the component analyte onto anadsorbent material. Evaluation can then be accomplished by desorbing theadsorbed analyte component, and determining the desorbed analytecomponent, or alternatively, by reacting the adsorbed material with adetection agent (e.g. indicating agent) to form a detectable species,and then detecting the presence, absence or relative or absolutequantity of the detectable species.

Such methods can be further characterized with respect to thecandidate-material evaluation throughput. For example, the candidatematerials can be evaluated for catalytic activity (e.g. yield) at athroughput of not less than about I candidate material/hour. Inpreferred applications, the throughput can be not less than about 1candidate material/second.

In some applications, these methods of the invention can furthercomprise unloading the reactant-contacted candidate materials from themicroreactors in which they reside, and then loading a second set of atleast four different candidate materials into the four or moremicroreactors of the chemical processing microsystem such that thesecond set of at least four different candidate materials areindividually resident in separate microreactors. Such reiterativeloading and unloading of candidate materials can be advantageouslyeffected using many of the chemical processing Microsystems ascharacterized above, with such features being employed alone or in anyof the various possible combinations.

The present invention is likewise directed to methods for evaluating oris optimizing process conditions for a chemical reaction of interest.Such methods generally comprise simultaneously supplying one or morereactants to each of four or more microreactors (where suchmicroreactors can be characterized as summarized above), controlling afirst set of reaction conditions to be substantially identical in eachof the microreactors, controlling a second set of reaction conditions tobe varied between two or more of the microreactors, simultaneouslydischarging a reactor effluent from each of the four or moremicroreactors, and evaluating the effect of varying the second set ofreaction conditions.

The invention is directed, moreover, to a distribution manifold fordistributing fluids in microfluidic systems. The manifold comprises acommon port adaptable for fluid communication with one or more fluidsources or sinks, 2^(n) terminal ports adaptable for fluid delivery toor fluid recovery from 2^(n) microcomponents, n being an integer notless than 2 and preferably not less than 6, and a distribution channelproviding fluid communication between the common port and each of the2^(n) terminal ports. The distribution channel comprises 2^(n)-1 channelsections, preferably linear channel sections, connected with each otherthrough 2^(n)-1 binary junctions. Each of the 2^(n)-1 channel sectionshas at least three access ports serving as the common port, as aconnection port for a binary junction, or as a terminal port. The 2^(n)microcomponents are preferably arranged in a substantially planar arraywith a planar density of not less than about 1 microcomponent/cm².

The invention is, in another case, directed to methods for providingfluids to or removing fluids from a plurality of microcomponents. Thesemethods comprise simultaneously supplying a fluid to, or discharging afluid from, each of 2^(n) microcomponents, where n is an integer of notless than 2, and preferably not less than 6. The fluid is supplied ordischarged through a distribution manifold having features as summarizedin the immediately preceding paragraph.

The present invention is still further directed to a microreactor formicroscale chemical reactions. The microreactor comprises a surfacedefining a reaction cavity for carrying out a chemical reaction, aninlet port in fluid communication with the reaction cavity for supplyingone or more reactants thereto, and an outlet port in fluid communicationwith the reaction cavity for discharging one or more reaction productstherefrom. The reaction cavity has a volume of not more than about 10 μland a geometry defined by ratios of distances X, Y, and Z measuredwithin the reaction cavity along three mutually orthogonal lines havinga common point of intersection at a midpoint of the longest line, Z,with the longest line, Z, being normal to at least one surface withwhich it intersects and, where allowed by the geometry, with at leasttwo surfaces with which it intersects. The reaction cavity geometry ischaracterized by ratios of X:Z and Y:Z each ranging from about 1:2 toabout 1:1.

The present invention is directed, as well, to methods for effecting amicroscale chemical reaction. One or more reactants for a chemicalreaction of interest are supplied to a microreactor comprising a surfacedefining a reaction cavity having a volume of not more than about 10 μlfor carrying out a chemical reaction, an inlet port in fluidcommunication with the reaction cavity for supplying one or morereactants thereto, and an outlet port in fluid communication with thereaction cavity for discharging one or more reaction products therefrom.The reactants reside in the reaction cavity under process conditionseffective for the chemical reaction of interest for a residence time,τ_(res,) that is longer than the diffusion period, τ_(diff), for thereaction cavity under such process conditions, and the reactants arethereby converted to one or more reaction products in the reactioncavity.

As such, the devices, systems, and methods of the present inventionoffer distinct advantages over the prior-art. The chemical processingMicrosystems of the present invention provide efficient means forloading and unloading candidate materials being evaluated, for supplyingreactants to a plurality of microreactors, for controlling of thereaction conditions in a plurality of microreactors, and for evaluatingthe candidate materials for specific properties of interest (e.g.,catalytic activity). Additionally, the instant chemical processingMicrosystems can be employed for screening candidate materials such ascatalysts with very high-throughput and with a large degree ofanalytical flexibility. Moreover, the chemical processing Microsystemsof the invention require only a small amount of candidate materialsrelative to known systems, yet offer catalyst contact times that aregenerally representative of those employed in production-scale reactors.Advantageously, the contact-time distribution is, for one embodiment ofmicroreactors, broader than the distribution associated with knownmicroreactor designs, and is, therefore, better suited to acombinatorial primary screen than known designs. Additionally, thechemical processing microsystems of the present invention can berelatively inexpensively manufactured using commercially availabletechnologies.

The devices, systems and methods of the invention have a primaryapplication in the field of combinatorial materials science research foridentifying and optimizing new materials that enhance chemicalprocesses. Nonetheless, many of such devices, systems and methods willalso find applications in other areas, such as combinatorial chemistrygenerally (including pharmaceutical and biotechnological applications),process characterization and optimization and small-quantity, end-usemanufacturing (for example, of hazardous chemicals among others).

Other objects, features and advantages of the present invention will bein part apparent to those skilled in the art and in part pointed outhereinafter. All references cited herein, whether as part of thebackground or as part of the detailed description, are incorporatedherein by reference for all purposes. Moreover, as the patent andnon-patent literature relating to the subject matter disclosed and/orclaimed herein is substantial, many relevant references are available toa skilled artisan that will provide further instruction with respect tosuch subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A through FIG. 1C are schematic diagrams showing the general stepsfor identifying and/or optimizing materials that enhance a chemicalprocess (FIG. 1A), as well as more specific, preferred approaches (FIG.1B) and embodiments (FIG. 1C) for the same.

FIG. 2 is a cross-sectional side view of an exemplary embodiment of achemical processing microsystem comprising an array of solid-phasecandidate materials.

FIG. 3A through FIG. 3H are partial cross-sectional side views showingexemplary configurations of arrays of candidate materials. As shown, thecandidate materials are formed as one or more films on various exposedsurfaces of a substrate (FIG. 3A through FIG. 3D), are included withinan array linked to a porous-substrate (FIG. 3E, FIG. 3F) or linked tomicroparticles (FIG. 3G, FIG. 3H), or are included in the array as bulkcandidate materials (FIG. 3G, FIG. 3H).

FIG. 4A through FIG. 4E are partial cross-sectional side views showing anumber of variations with respect to the geometry with which an array ofcandidate materials can be integrated with other laminae to form anarray of candidate-material loaded microreactors.

FIG. 5 is a partial cross-sectional side view showing a plurality ofnon-planar microreactors formed in a plurality of laminae.

FIG. 6A and FIG. 6B are, respectively, a top plan view of asubstantially planar wafer substrate for an array of 256 candidatematerials (FIG. 6A), and a partial-cross-sectional side view of anindividual well formed in one surface of the wafer substrate (FIG. 6B)into which candidate materials can be deposited.

FIG. 7A through FIG. 7I are views of various exemplary embodiments offluid-distribution systems that can be used for fluid communicationbetween a plurality of microcomponents and an external fluid sources ofsinks. FIG. 7A is a top-plan view of a typical fluid distributionmanifold. FIG. 7B is a top-plan view of preferred binary-tree fluiddistribution manifolds serving an array of 256 microreactors. FIGS. 7Cand 7D are perspective views of ternary and quaternary fluiddistribution manifolds, respectively, serving 27 and 64 microcomponents,respectively. FIG. 7E is a top-plan view showing one flow-path of thebinary-tree distribution manifold of FIG. 7B (rotated about 90°clockwise from its orientation in FIG. 7B). FIG. 7F is a top-plan viewof a microreactor having inlet and outlet ports in fluid communicationwith the distribution manifolds. FIG. 7G and FIG. 7H are top plan viewsof other fluid distribution systems serving chemical processingmicrosystems having microreactors and microseparators integrated onto asingle, substantially planar wafer substrate. More specifically, FIG. 7Gshows a partial-binary supply manifold serving 32 microreactors,interconnecting manifolds to 32 dedicated microseparators and apartial-binary separator effluent manifold. FIG. 7H shows a binary-treesupply manifold serving 128 microreactors, interconnecting manifolds to128 dedicated microseparators and a binary-tree separator effluentmanifold. FIG. 7I is a top-plan view of another preferred binary-treefluid distribution manifold serving an array of 256 microreactors andhaving a single common inlet port 510 situated near the peripherythereof FIG. 8 is a partial cross-sectional side view of a plurality oflaminae having a candidate-material containing microreactor formedtherein.

FIG. 9A through FIG. 9I are partial cross-sectional side views ofvarious laminae showing intermediate composite structures during thefabrication of a microreactor shown in FIG. 8.

FIG. 10A through FIG. 10I are partial cross-sectional side views ofvarious laminae taken at line I-I of FIGS. 9A through 10A, respectively.

FIG. 11A through FIG. 11F are perspective views of variousthree-dimensional geometries having XYZ coordinates superimposedtherein, including a sphere (FIG. 11A), a cube (FIG. 1B), a parallelpiped (FIG. 11C), a tube (FIG. 11D), a relatively flat cylinder (FIG.11E) and parallel plates (FIG. 11F).

FIG. 12 is a graph showing reaction temperatures and residence (contact)times for effecting various exemplary heterogeneously-catalyzedreactions of commercial significance using known commercial catalysts.

FIG. 13A through FIG. 13C are graphs showing residence-time probabilityfunctions for an ideal plug-flow reactor (PFR) (FIG. 13A), for apractical PFR (FIG. 13B) and for a continuous-stirred-tank reactor(CSTR) (FIG. 13C).

FIG. 14 is a top-plan view of preferred binary-tree distributionmanifolds serving an array of 256 microcomponents, suitable for example,for use as a microreactor discharge manifold in connection with thechemical processing microsystem of FIG. 8 or as a microseparatoreffluent manifold in connection with the chemical processing microsystemof FIG. 18A.

FIG. 15A through FIG. 15C are partial cross-sectional side views showingexemplary configurations of arrays of adsorbent materials. As shown,adsorbent materials are formed as one or more films on various exposedsurfaces of a substrate without temperature control (FIG. 15A), with atemperature-control block (FIG. 15B) or with dedicated heating elements(FIG. 15C).

FIG. 16A through FIG. 16E show various configurations for arrays ofadsorbent materials. FIGS. 16A and 16B show, respectively, a top planview of a substantially planar wafer substrate for an array of 256adsorbent materials (FIG. 16A), and a partial-cross-sectional side viewof an individual well formed in one surface of the wafer substrate (FIG.16B) into which the adsorbent materials can be deposited. FIG. 16C is atop plan view of an array of substantially parallel thin-layerchromatography (TLC) channels comprising adsorbent material and beingadapted for fluid communication with distribution systems for amobile-phase eluant. FIG. 16D shows a top plan view of a substantiallyplanar wafer substrate for an array of 128 microreactors with aneffluent distribution manifold that allows for adsorption of effluentcomponents onto adsorbent material provided in microseparators (900)arranged in a row near the periphery of the wafer. FIG. 16E shows a topplan view of a substantially planar wafer having an array ofmicroseparators arranged in a row to correspond with an row ofaperatures (519 of FIG. 16D), and in fluid communication therewith.

FIG. 17A and FIG. 17B are partial cross-sectional side views showing aalternatives with respect to the geometry with which an array ofadsorbent materials and an array of candidate materials can beintegrated with other laminae to form an array of candidate-materialloaded and adsorbent-material containing microreactors.

FIG. 18A through FIG. 18J show several embodiments for a chemicalprocessing microsystem. FIG. 18A and FIG. 18B are, respectively, apartial cross-sectional side view of a modular chemical processingmicrosystem (FIG. 18A) having a plurality of microreactors and aplurality of microseparators formed in a plurality of laminae, and aperspective view of a partially-assembled housing (FIG. 18B) adaptablefor assembly and operation of the modular chemical processingmicrosystem of FIG. 18A. FIGS. 18C and 18D show, respectively, anadditional perspective view (FIG. 18C) and a corresponding sidesectional view (taken at A-A) (FIG. 18D) of a partially-assembledhousing and microsystem. Various subcomponents of the chemicalprocessing microsystem of FIGS. 18C and 18D are shown in FIGS. 18Ethrough 18I, including: a bottom plan view of a first microreactorsupport block (FIG. 18E), a perspective view of an external fluiddistribution subassembly (FIG. 18F), a perspective view (FIG. 18G) and acorresponding cross-sectional view (taken at B-B) (FIG. 18H) of a fluiddistribution subassembly and a schematic diagram (FIG. 18I) for theextneral fluid distribution subassembly. FIG. 18J is a schematic diagramfor a modular chemical processing microsystem that includes a pluralityof “flow-through” microreactors.

FIG. 19A through FIG. 19C are partial cross-sectional views ofadsorbent-containing arrays with various configurations of detectionprobes and heaters.

FIG. 20A through FIG. 20F show data resulting from the operation of oneembodiment of the chemical processing microsystem of the invention, asdescribed in connection with Example 2. FIG. 20A is a graph showing acalibration plot of integrated intensity of fluorescence measured usinga CCD camera against various amounts of a known analyte. FIG. 20B is agraph showing detector output (integrated fluorescence intensitymeasured using a CCD camera versus catalyst loading (mass fraction oftotal catalyst) in the reaction cavities of various microreactors. FIG.20C is an output image showing detector output (fluorescence intensity)measured using a CCD camera for operation of the integrated parallelmicroreactor/microseparator system with catalysts loaded only in certainmicroreactors (demonstrating a lack of substantial cross-talk betweenadjacent microreactors). FIGS. 20D through 20F each show output images(fluorescence intensity) measured using a CCD camera for experimentsdirected toward identifying and optimizing catalysts for a particularreaction of interest, where compositional variations were explored usingternary libraries of noble metals (NM) and transition metals (TM) (FIG.20D), ternary libraries of noble metals (NM) and dopants (D) (FIG. 20E),and ternary libraries of promising catalysts identified from theseexperiments with various catalyst support materials (FIG. 20F).

The invention is described in detail below with reference to thefigures, in which like items are numbered the same in each of theseveral figures.

DETAILED DESCRIPTION OF THE INVENTION

In the present invention, a chemical processing microsystem havingfeatures that enable an effective combinatorial materials scienceresearch program is provided. Such a research program may be directed,for example, to identifying or optimizing materials that enhance achemical process, or to other research goals, such as processcharacterization or optimization. The systems, devices and methodsdisclosed herein can also be adapted to the production of smallquantities of chemicals.

Among the several significant aspects of the present invention,approaches and devices are presented for efficiently loading, unloadingand/or reloading a plurality of different materials into and out of aplurality of microreactors—for screening of the materials as candidatesfor a capability to enhance a chemical process. In one embodiment, thechemical processing microsystem can include a plurality of microreactorsfor carrying out a chemical process of interest, and integral therewith,an array of two or more materials known to enhance or being screened fora capability to enhance the chemical process. At least a portion of amaterial-containing region of the array is within each (or most) of themicroreactors (exceptions being, for example, for control microreactorsthat may not have such a material included therein). Significantly, thearray of materials can be readily and conveniently added to or removedfrom the other structural elements that define the chemical processingmicrosystem, such that different arrays can be interchanged with eachother, with minimal effort, and without substantially affecting thestructural integrity of the other structural elements of the chemicalprocessing microsystem. The interchangeability of different arrays ofmaterials into a chemical processing microsystem allows for thesimultaneous loading of the various candidate materials to the pluralityof microreactors, and, after the chemical reaction has been effected,simultaneous unloading therefrom. Significantly, therefore, theinterchangeable arrays, particularly arrays that include over 250different candidate materials, enable a researcher to screen a verylarge number of candidate materials in a relatively short period oftime, in a cost-effective manner. Such interchangeable arrays are alsoadvantageous for screening more moderate numbers of candidate materials.

In another aspect of the chemical processing microsystem of theinvention, approaches and devices are disclosed for efficientlysupplying reactants to each of a plurality of microreactors and forestablishing reaction conditions in each of the plurality ofmicroreactors that are substantially identical or, in alternativeembodiments, that are controllably varied between microreactors. In apreferred embodiment, the fluid distribution manifold for fluidcommunication between each of a plurality of parallel microreactors anda common external fluid source or sink is designed such that thepressure is the same at each microreactor inlet and the volumetric flowrate is the same through each microreactor. Distribution manifoldshaving such equi-flow and equi-pressure characteristics can be achievedby providing flow paths having equal conductance—for example, flow pathsof equal length and equivalent geometry—from the common port to each ofthe microreactors. Such design objectives, while perhaps straightforwardfor chemical processing Microsystems having relatively few microreactorsand/or for chemical processing Microsystems that are unconstrained withrespect to space considerations, present substantial engineeringchallenges for chemical processing Microsystems having greater than tenmicroreactors and/or having a planar microreactor concentration ofgreater than about 5 microreactors/cm².

In a further aspect the invention, the chemical processing microsystemcan include a diffusion-mixed microreactor. The diffusion-mixedmicroreactor is designed such that when operating as a continuous flowreactor—where one or more reactants for a chemical reaction of interestis continuously supplied to the microreactor, the reaction occurstherein under process conditions effective for the chemical reaction ofinterest, and a reaction effluent stream is continuously dischargedtherefrom—the reactants reside in the reaction cavity for a residencetime, τ_(res,) that is longer than the diffusion period, τ_(diff), forthe reaction cavity under such process conditions. As such, mixing ofreactants is achieved on a microscopic level without an active mixingmicrocomponent. Significantly, the continuous diffusion-mixedmicroreactor is representative of and can be used to model, on amicroscopic scale, a continuous stirred-tank reactor (CSTR). Suchdiffusion-mixed microreactors are advantageous over channel-typemicroreactors (including microreactors having tortuous channels toeffect passive mixing), because complete mixing can occur within a muchsmaller volume. This advantage has substantial implications forcombinatorial research (e.g., directed to heterogeneously catalyzedreactions) because a much smaller amount of each of the plurality ofmaterials (e.g., catalysts) is required to effect the experiment.Moreover, the diffusion-mixed microreactors offer a broader distributionof residence times than channel-type microreactors designed to modelplug-flow reactors. As discussed in detail below, such a broaderdistribution of residence times can be advantageous in combinatorialmaterial research applications—particularly for use as a primary screen.

As an additional aspect of the invention, the chemical processingmicrosystem can be configured with flexibility to employ a wide varietyof instrumentation for determining the extent to which the chemicalreaction of interest occurs in each of the microreactors. Suchanalytical determinations are important for evaluating a candidatematerial or for characterizing or optimizing the chemical reaction ofinterest. The analytical determinations can be carried out by in situsampling in the microreactor, or alternatively, by discharging areaction effluent stream comprising one or more reaction products formedby the reaction of interest, if any, and unreacted gaseous reactants, ifany, from each of the microreactors to the analytical instrumentation.In the latter case, the reaction effluent can be dischargedsimultaneously (in parallel) or sequentially (in rapid serial) from eachmicroreactor. The analytical instrumentation could be completelyintegral with the chemical processing microsystem, partially integraltherewith, or completely independent therefrom. In a preferred,partially integrated embodiment, the reaction effluent is dischargedfrom each of the microreactors to dedicated separation chambers, eachseparation chamber having, integral therewith, an adsorbent material foradsorbing at least one of the reaction products and/or unreacted gaseousreactants. The adsorbent materials are preferably on a common substratethat can be readily and conveniently added to or removed from the otherstructural elements that define the chemical processing microsystem,such that different adsorbent-containing substrates can be interchangedwith each other, with minimal effort, and without substantiallyaffecting the structural integrity of the other structural elements ofthe chemical processing microsystem. The interchangeability of theadsorbent-containing substrates into a single chemical processingmicrosystem allows for simultaneous, parallel separation of one or moreof the various reaction products and/or excess reactants. Suchinterchangeability also allows for simultaneously fixing or recordingthe results of the screening in a physical form, such that theanalytical determination can be completed at a different location and ata later time in parallel or serial fashion, thereby freeing the chemicalprocessing microsystem for screening the next array of candidatematerials, and improving overall throughput.

These and other aspects of the invention are discussed in greater detailbelow. The several aspects of the chemical processing microsystemdisclosed and claimed herein can be advantageously employed separately,or in combination to identify and optimize materials that enhancechemical processes, to characterize and optimize chemical processes, andif desired, to prepare microamounts of chemicals. In preferredembodiments, these features are employed in combination to form achemical processing microsystem that can operate as a primary screen orsecondary screen in a materials science research program directed toidentifying and optimizing new materials such as heterogeneouscatalysts.

Identifying/Optimizing Materials that Enhance a Chemical Process

A large number of chemical processes are enhanced by materials. Thecatalysis of chemical reactions is exemplary, and of substantialcommercial significance. Additionally, however, other processes—such asseparations and other unit operations that affect the chemical orphysical state of a material of interest—can likewise be enhanced bymaterials. For example, adsorbents that-are selective for a particularspecies can enhance the separation of that species from a mixtureincluding the species. As another example, stabilizers used in chemicalcompositions can impact the rate of decomposition of such compositions,ultimately affecting the shelf-life thereof. Likewise, blocking moietiesor scavengers can enhance the yield of a chemical reaction of interestby retarding an undesirable side reaction. Hence, while details of thepresent invention are primarily described herein in connection with thecatalysis of chemical reactions and, particularly, in connection withheterogeneous catalysis, such applications should be consideredexemplary and non-limiting with respect to other potential applicationsof the invention. Moreover, while much of the discussion presentedherein is directed toward identifying materials (e.g., catalysts) thatenhance a certain specific reaction of interest, the devices, systemsand approaches disclosed herein can likewise be directed towardidentifying which reactions are enhanced (e.g., catalyzed) by a certainspecific material (e.g., catalyst) of interest.

According to one approach for identifying such useful materials, a largecompositional space of potential candidate materials may be rapidlyexplored through the preparation and evaluation of candidate materiallibraries. Such candidate material libraries can comprise, for example,compositional gradients of two or more components, such as binarycompositional gradients of components A and B, ternary compositionalgradients of components A, B, and C, or higher-order compositionalgradients. Candidate material libraries could alternatively comprisecompounds having a number of structural variations relative to a basecompound, such that the compounds in the library share a commonstructural scaffold.

In an initial, primary screening, candidate materials can be rapidlyevaluated over a large compositional space according to the systems,devices and methods of the present invention to provide valuablepreliminary data and, optimally, to identify several “hits”—particularcandidate materials having characteristics that meet or exceed certainpredetermined metrics (e.g., performance characteristics, properties,etc.). Such metrics may be defined, for example, by the characteristicsof the then best known material for the chemical process of interest.The first candidate material libraries run through a primary screeningcan comprise, for example, full-range compositional gradients havingcompositional ratios ranging from 0% to 100% for each component. Becauselocal performance maxima may be located at compositions between thoseparticular compositions evaluated in the primary screening of the firstlibraries, it may be advantageous to screen more focused libraries(e.g., libraries focused on a smaller range of compositional gradients,or libraries comprising compounds having incrementally smallerstructural variations relative to those of the identified hits). Hence,the primary screen can be used reiteratively to explore localized and/oroptimized compositional space in greater detail. The preparation andevaluation of more focused libraries can continue as long as thehigh-throughput primary screen can meaningfully distinguish betweenneighboring library compositions or compounds.

Once one or more hits have been satisfactorily identified based on theprimary screening, libraries having candidate materials focused aroundthe primary-screen hits can be evaluated with a secondary screen—ascreen designed to provide (and typically verified, based on knownmaterials, to provide) chemical process conditions that may be scaled upwith a greater degree of confidence than those applied in the primaryscreen. Particular candidate materials having characteristics thatsurpass the predetermined metrics for the secondary screen may then beconsidered to be a “lead” material. If desired, additional librariescomprising candidate materials focused about such lead materials can bescreened with additional secondary screens. Identified lead materialsmay be subsequently developed for commercial applications throughtraditional bench-scale and/or pilot scale experiments.

While the concept of primary screens and secondary screens as outlinedabove provides a valuable combinatorial research model for manymaterials of interest and for many chemical processes, a secondaryscreen may not be necessary for certain chemical processes where primaryscreens provide an adequate level of confidence as to scalability and/orwhere market conditions warrant a direct development approach.Similarly, where optimization of materials having known properties ofinterest is desired, it may be appropriate to start with a secondaryscreen. In general, the systems, devices and methods of the presentinvention may be applied as either a primary or a secondary screen forone or more libraries of candidate materials, to identify candidatematerials that enhance the chemical process of interest.

According to the present invention, methods, systems and devices aredisclosed that improve the efficiency and/or effectiveness of the stepsnecessary to screen multiple libraries of candidate materials. Withreference to FIG. 1A, screening a library of candidate materials for acapability to enhance a chemical reaction of interest requires (A)supplying different candidate materials to different microreactors, (B)providing reactants to the microreactors, (C) controlling reactionconditions in each microreactor to effect the chemical reaction ofinterest in the presence of the candidate material, and (D) evaluatingeach of the candidate materials with respect to their capability forenhancing the chemical reaction. If the microreactors are to operate asa continuous reactor, rather than as a batch reactor, then screeningwill also require (E) discharging reaction products, if any, and excessreactants, if any, from the microreactors. Except where themicroreactors used for such screening are considered to be“single-load”, disposable systems, or where the same library ofcandidate materials will be rescreened (e.g., under different reactionconditions), reuse of the same microreactors for screening a secondlibrary of candidate materials will also require (F) removing thecandidate materials that had been exposed to the reaction conditionsfrom each of the microreactors. Once the exposed candidate materials areremoved from each of the microreactors, steps (A) through (D),optionally step (E), and preferably step (F) can be repeated, asnecessary.

Each of the steps, (A) through (F), depicted in FIG. 1A can beoptimized, individually or in combination, to effect a high-throughputresearch program for identifying reaction-enhancing materials such ascatalysts. As a general approach, each of the steps (A) through (F) canbe done in parallel for the plurality of candidate materials andrespective microreactors. Moreover, each of the individual steps (A)through (F) can, where possible, be performed concurrently with othersof such steps during the same cycle of steps, or where possible,performed after a first cycle of steps is complete, and concurrentlywith a second cycle of steps (A) through (F). For example, withreference to FIGS. 1A and 1B, in a preferred approach for screeningmultiple libraries of candidate materials (e.g., catalysts) using thesame set of microreactors, the fresh candidate materials are suppliedsimultaneously to each of the respective microreactors (step A),reactants (e.g., gas or liquid) are supplied simultaneously to each ofthe microreactors (either concurrently with or temporally separate fromthe supply of candidate materials) (step B), reactions are effected inparallel (step C), reaction products and unreacted reactants aredischarged simultaneously from each of the microreactors (step E), eachof the candidate materials are evaluated simultaneously (e.g., byadsorbent trapping of a reaction product and dye-based imaging, by gaschromatography and/or by mass spectroscopy among other approaches) (stepD), and/or the exposed candidate materials (e.g., catalysts) are removedsimultaneously from each of the microreactors (step F). Notable,simultaneous delivery and removal of each of the candidate materials totheir respective microreactors is advantageous in that differentlibraries of candidate materials can be quickly interchanged with themicroreactors, thereby improving overall throughput. It may also beadvantageous, with respect to overall throughput, to perform theevaluation step (D) concurrently with the reaction of interest using insitu measurement and analytical systems, and/or after the reaction ofinterest, but in parallel with or after the removal step (F). Forexample, with the proper analytical system, the evaluation step (D) fora first library of candidate materials can be performed while a secondlibrary of candidate materials is going through steps (A) through (C),and optionally steps (E) and (F).

In a preferred embodiment represented schematically in FIG. 1C, thechemical processing microsystem of the present invention is integratedinto a material evaluation system for effectively and efficientlyevaluating new materials such as catalysts. Briefly, a materialevaluation system 1 can comprise a chemical processing microsystem 10for simultaneously effecting a chemical process (e.g., reaction) ofinterest in the presence of a plurality of candidate materials (e.g.,catalysts) being evaluated, and, in preferred embodiments, forsimultaneously separating a characteristic component (e.g., reactionproduct) resulting from such process, a detection system 1000 forcharacterizing (e.g., quantitatively determining) such a characteristiccomponent, a material library handling system 5 for supplying andremoving entire libraries of candidate materials to and from thechemical processing microsystem 10 for screening therein, and a fluiddistribution system 480 for supplying fluids (e.g., reactants) to thechemical processing microsystem 10 and, except for batch processes, fordischarging fluids (e.g., reactor effluent stream) from the chemicalprocessing microsystem. The chemical processing microsystem 10 comprisesa plurality of microreactors 600 and, in a preferred embodiment, aplurality of microseparators 900 integral with the plurality ofmicroreactors. The microprocessors 600 are formed in a plurality oflaminae that include an interchangeable candidate-material array 100.The material array 100 comprises a plurality of different candidatematerials (e.g., catalysts), preferably arranged at separate,individually addressable portions of a substrate (e.g., wafer). Themicroseparators 900 are similarly formed in a plurality of laminae thatinclude an interchangeable adsorbent array 700. The adsorbent array 700comprises one or more adsorbents, preferably arranged at separate,individually addressable portions of a substrate to spatially correspondto the plurality of different candidate materials.

In operation, for example, in connection with research directed toidentifying new catalysts for a chemical reaction, a first materialarray 100 comprising a catalyst library is supplied to the plurality ofmicroreactors 600. Likewise, a first adsorbent array 700 comprising aplurality of adsorbent-containing regions is supplied to the pluralityof microseparators 900. The material array 100, and the adsorbent array700 are then each releasably engaged with and incorporated into theplurality of microreactors 600 and the plurality of microseparators 900,respectively. One or more reactants for the reaction of interest aresimultaneously supplied from the fluid distribution system 480 to theplurality of microreactors 600, and allowed to contact each of thedifferent candidate catalysts under reaction conditions effective (orintended to be effective) for the chemical reaction of interest. Aresulting reactor effluent stream is discharged simultaneously from eachof the plurality of microreactors, cooled if necessary, and thensupplied to the plurality of microseparators 900. One or more components(e.g., reaction products) of each of the reactor effluent streams areselectively adsorbed simultaneously onto the addressable regions of theadsorbent array 700, and the separated reactor effluent streams aresubsequently simultaneously discharged from the plurality ofmicroseparators. Following reaction and separation: (1) the firstadsorbent array 700 is disengaged from and removed from themicroseparators 900, and then transported, preferably automatically, tothe detection system 1000; and (if desired to change catalyst libraries)simultaneous therewith, (2) the first catalyst-containing material array100 is disengaged from and removed from the microreactors 600. A secondcatalyst library on a second material array 100′ and a second adsorbentarray 700′ can then be supplied to the chemical processing microsystem10 and the aforedescribed steps can be repeated with these arrays 100′,700′. The first adsorbate-containing adsorbent array 700 can becharacterized in the detection system 1000 while the second library ofcatalyst material 100′ is being screened, or, if desired, at a latertime and/or at a remote location.

Further aspects of the material evaluation system 1, as well assubsystems thereof and operational aspects thereof, are described below.

Candidate Materials

Each of the candidate materials being screened for a capability toenhance a chemical process of interest can be an element, a compound ora composition comprising a plurality of elements and/or compounds. Thecandidate material can be in a gaseous, liquid or solid phase.Solid-phase candidate materials are preferred for some applications. Theparticular elements, compounds or compositions to be included in alibrary of candidate materials will depend upon the particulars of thechemical process being investigated. As noted above, however, theparticular chemical process being investigated is not critical, and caninclude chemical reactions and chemical separations among others.

The chemical process is preferably a chemical reaction, which forpurposes. thereof, means a process in which at least one covalent bondof a molecule or compound is formed or broken. As such, immunoreactionsin which immunoaffinity is based solely on hydrogen bonding or otherforces—while chemical processes—are not considered to be chemicalreactions. In general, the candidate materials of this inventioncatalyze reactions that include activation of, breaking and/or formationof H—Si, H—H, H—N, H—O, H—P, H—S, C—H, C—C, C═C, C≡C, C-halogen, C—N,C—O, C—S, C—P, C—B and C—Si bonds among others. Exemplary chemicalreactions for which reaction-enhancing materials may be identifiedaccording to the present invention include, without limitation,oxidation, reduction, hydrogenation, dehydrogenation (including transferhydrogenation), hydration, dehydration, hydrosilylation, hydrocyanation,hydroformylation (including reductive hydroformylation), carbonylation,hydrocarbonylation, amidocarbonylation, hydrocarboxylation,hydroesterification, hydroamination, hetero-cross-coupling reaction,isomerization (including carbon-carbon double bond isomerization),dimerization, trimerization, polymerization, co-oligomerization (e.g.CO/alkene, CO/alkyne), co-polymerization (e.g. CO/alkene, CO/alkyne),insertion reaction, aziridation, metathesis (including olefinmetathesis), carbon-hydrogen activation, cross coupling, Friedel-Craftsacylation and alkylation, Diels-Alder reactions, C—C coupling, Heckreactions, arylations, Fries rearrangement, vinylation, acetoxylation,aldol-type condensations, aminations, reductive aminations,epoxidations, hydrodechlorinations, hydrodesulfurations andFischer-Tropsch reactions, asymmetric versions of any of theaforementioned reactions, and combinations of any of the aforementionedreactions in a complex reaction sequence of consecutive reactions. Forchemical reactions, the candidate materials can be generally classifiedas those materials which are chemically altered or consumed during thecourse of the reaction (e.g., co-reactant materials, cataloreactants)and those materials which are not chemically altered or consumed duringthe course of the reaction (e.g., catalysts, selective blockingmoieties). In preferred applications, the candidate materials arecatalysts. As used herein, the term catalyst is intended to include amaterial that enhances the reaction rate of a chemical reaction ofinterest or that allows a chemical reaction of interest to proceed wheresuch reaction would not substantially proceed in the absence of thecatalyst.

The candidate materials preferably comprise elements or compoundsselected from the group consisting of inorganic materials, metal-ligandsand non-biological organic materials. In some applications, thecandidate materials will consist essentially of inorganic materials,consist essentially of metal-ligand materials, or consist essentially ofnon-biological organic materials. Moreover, in some applications, thecandidate materials will be compositions comprising mixtures ofinorganic materials, metal-ligand materials, and/or non-biologicalorganic materials in the various possible combinations.

Inorganic materials include elements (including carbon in its atomic ormolecular forms), compounds that do not include covalent carbon-carbonbonds (but which could include carbon covalently bonded to otherelements, e.g., CO₂), and compositions including elements and/or suchcompounds. Inorganic candidate materials that could be investigatedaccording to the approaches described herein include, for example: noblemetals such as Au, Ag, Pt, Ru, Rh, Pd, Ag, Os and Ir; transition metalssuch as Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Ta, W and Re;rare-earth metals such as La, Ce, Pr, Nd, Sm, Eu, Th, Th and U; alloysof noble metals, transition metals and/or rare-earth metals; metaloxides such as CuO, NiO and Co₃O₄; noble-metal-doped metal oxides suchas noble-metal-doped CuO, NiO and Co₃O₄; multi-metal oxides such asbinary oxides of Cu—Cr, Cu—Mn, Cr—Mn, Ni—Cr, Ni—Mn, Ni—Cu, Ni—Mo, Cu—Mo,Ni—Co, Co—Mo, Ni—Fe, Fe—Mo, Cu—Fe, Mn—Ag, Mn—Sn, Ag—Sn, Cu—Ag, Cu—V,Ag—V, Cu—V, Ni—V, Bi—Mo, Bi—V, Mo—V, V—Zr, V—Ti, Zr—Ti, V—Nb, Nb—Mo,V—P, P—Mo, Ni—P, P—Cu, Co—P, Co—Fe, P—Fe, Mg—V, Mg—Sn, V—Sn, K—Ti, K—Bi,Ti—Bi, Cr—Sb, Cr—V, Sb—V, Bi—Mo, Bi—Nb, K—Cr, K—Al, Al—Cr, Zn—Cu, Zn—Al,Cu—Al, La—Cr, La—Zr, Cr—Zr, La—Mo, Mo—Zr, La—W, W—Zr, Mo—W, W—V, Cu—W,Bi—W, Fe—Sb, Fe—V and Ni—Ta, Ni—Nb and Ta—Nb, and such as ternary oxidesof Cu—Cr—Mn, Ni—Cr—Mn, Ni—Cu—Mo, Ni—Co—Mo, Ni—Fe—Mo, Cu—Fe—Mo, Mn—Ag—Sn,Cu—Ag—V, Cu—Ni—V, Bi—Mo—V, V—Zr—Ti, V—Nb—Mo, V—P—Mo, Ni—P—Cu, Co—P—Fe,Mg—V—Sn, K—Ti—Bi, Cr—Sb—V, Bi—Mo—Nb, K—Cr—Al, Zn—Cu—Al, La—Cr—Zr,La—Mo—Zr, La—W—Zr, Mo—W—V, Cu—Mo—W, Bi—Mo—W, Bi—V—W, Fe—Sb—V andNi—Ta—Nb; metal carbides such as PdC; metal sulfates, metal sulfides,metal chlorides, metal acetates, polyoxometallates (POM); metalphosphates such as vanadylpyrophosphates (VPO); Bronstead acids such asHF; Lewis Acids such as AlCl₃; and mixtures of any of the aforementionedinorganic materials, among others. Exemplary inorganic materiallibraries could include, for example, a triangular-shaped array ofternary metal oxides (e.g. such as oxides of the ternary metal partnersdescribed above) with single metal oxide compounds at each corners,binary metal oxide compositions along each of the sides with varyingratios of constituents, and ternary metal oxide compositions in theinterior regions of the triangular array with varying ratios ofconstituents. Libraries of inorganic candidate materials can beprepared, for example, according to the methods disclosed in U.S. Pat.No. 5,776,359 to Schultz et al.

Metal-ligands comprise a central metal atom or ion surrounded by,associated with and/or bonded to other atoms, ions, molecules orcompounds—collectively referred to as “ligands”—typically through acarbon (to form, e.g., an organometallic), nitrogen, phosphorous, sulfuror oxygen atom and/or one or more linker moieties. The one or moreligands typically bind to one or more metal center and/or remainassociated therewith, and by such association, modify the shape,electronic and/or chemical properties of the active metal center(s) ofthe metal-ligand complex. The ligands can be organic (e.g., η¹-aryl,alkenyl, alkynyl, cyclopentadienyl, CO, alkylidene, carbene) orinorganic (e.g., Br⁻, Cl⁻, OH⁻, NO²⁻, etc.), and can be charged orneutral. The ligand can be an ancilliary ligand, which remainsassociated with the metal center(s) as an integral constituent of thecatalyst or compound, or can be a leaving group ligand, which may bereplaced with an ancillary ligand or an activator component. Exemplarymetals/metal ions include ions derived from, for example, simple salts(e.g., AlCl₃, NiCl₂, etc.), complex or mixed salts comprising bothorganic and inorganic ligands (e.g., [({acute over (η)}5-C₅Me₅)IrCl₂]₂,etc.) and metal complexes (e.g., Gd(NTA)₂, CuEDTA, etc.), and cangenerally include, for example, main group metal ions, transition metalions, lanthanide ions, etc.

Libraries of metal-ligand candidate materials can be prepared, forexample, according to the methods disclosed in PCT Patent Application WO98/03521 of Weinberg et al. Briefly, a desired ligand can be combinedwith a metal atom, ion, compound or other metal precursor compound. Inmany applications, the ligands will be combined with such a metalcompound or precursor and the product of such combination is notdetermined, if a product forms. For example, the ligand may be added toa reaction vessel at the same time as the metal or metal precursorcompound along with the reactants. The metal precursor compounds may becharacterized by the general formula M(L)_(n) (also referred to asML_(n) or M-L_(n)) where M is a metal and can include metals selectedfrom the group consisting of Groups 5, 6, 7, 8, 9 and 10 of the PeriodicTable of Elements. In some embodiments, M can be selected from the groupconsisting of Ni, Pd, Fe, Pt, Ru, Rh, Co and Ir. L is a ligand and canbe selected from the group consisting of halide, alkyl, substitutedalkyl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substitutedheterocycloalkyl, aryl, substituted aryl, heteroaryl, substitutedheteroaryl, alkoxy, aryloxy, hydroxy, boryl, silyl, hydrido, thio,seleno, phosphino, amino, and combinations thereof, among others. When Lis a charged ligand, L can be selected from the group consisting ofhydrogen, halogens, alkyl, substituted alkyl, cycloalkyl, substitutedcycloalkyl, heteroalkyl, heterocycloalkyl, substituted heterocycloalkyl,aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,aryloxy, silyl, boryl, phosphino, amino, thio, seleno, and combinationsthereof. When L is a neutral ligand, L can be selected from the groupconsisting of carbon monoxide, isocyanide, nitrous oxide, PA₃, NA₃, OA₂,SA₂, SeA₂, and combinations thereof, wherein each A is independentlyselected from a group consisting of alkyl, substituted alkyl,heteroalkyl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl,substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl, alkoxy, aryloxy, silyl, and amino. Specificexamples of suitable metal precursor compounds include Pd(dba)₂(dba=dibenzylydieneacteone), Pd₂(dba)₃, Pd(OAc)₂ (Ac=acetate), PdCl₂,Pd(TFA)₂, (TFA=trifluoroacetate), (CH₃CN)₂PdCl₂, and the like. In thiscontext, the ligand to metal precursor compound ratio is in the range ofabout 0.01:1 to about 100:1, more preferably in the range of about 0.5:1to about 20:1. The metal atom, ion or metal precursor may be supportedor not. Supports may be organic or inorganic. Similar to the ligands,the support may be an L. In other embodiments, the support will not formpart of the metal precursor and suitable supports include silicas,aluminas, zeolites, polyethyleneglycols, polystyrenes, polyesters,polyamides, peptides and the like. Specific examples of Pd supportedmetals include Pd/C, Pd/SiO₂, Pd/CaCO₃, Pd/BaCO₃, Pd/aluminate,Pd/aluminum oxide, Pd/polystyrene, although any of the metals listedabove could replace Pd in this list, e.g., Ni/C, etc. In otherapplications, the ligand will be mixed with a suitable metal precursorcompound prior to or simultaneous with allowing the mixture to becontacted to the reactants. When the ligand is mixed with the metalprecursor compound, a metal-ligand complex may be formed, which may beemployed as a candidate material.

Non-biological organic materials include organic materials other thanbiological materials. Organic materials are considered to includecompounds having covalent carbon-carbon bonds. Biological materials areconsidered to include nucleic acid polymers (e.g., DNA, RNA) amino acidpolymers (e.g., enzymes) and small organic compounds (e.g., steroids,hormones) where the small organic compounds have biological activity,especially biological activity for humans or commercially significantanimals such as pets and livestock, and where the small organiccompounds are used primarily for therapeutic or diagnostic purposes.While biological materials are of immense commercial interest withrespect to pharmaceutical and biotechnological applications, a largenumber of commercially significant applications involve chemicalprocesses that are enhanced by other than biological materials.Moreover, while fundamental screening approaches for many pharmaceuticaland biological activities are known or readily adapted from knownapproaches, screening approaches for non-biological materials have notheretofore been widely investigated and reported. Although the candidatematerials being screened are preferably not, themselves, biologicalorganic materials, the candidate materials of the invention (e.g.,inorganic materials) can be employed to enhance reactions directed toproducing a biological organic material as the product of a chemicalreaction (e.g., materials that enhance chemical-based, non-enyzmatic DNAsynthesis, or materials that enhance a synthetic, non-enyzmatic route toa particular hormone or steroid).

In preferred applications, the candidate materials are catalysts beingscreened for catalytic activity and/or for catalytic selectivity for achemical reaction of interest. The candidate catalysts can behomogeneous catalysts or heterogeneous catalysts. For homogeneouscatalysis, the candidate materials are preferably solids or liquidswhich are soluble or miscible in the reaction medium under the reactionconditions, but can also include gasses. For heterogeneous catalysis,the candidate materials are preferably solids. In general, homogeneouscandidate catalyst materials and heterogeneous candidate catalystmaterials can include organic, inorganic and metal-ligand catalysts suchas are described above. Exemplary reactions for which a homogeneouscatalyst may be investigated pursuant to the present invention, as wellas known homogeneous catalysts for such reactions are shown in Table 1A.Exemplary reactions for which a heterogeneous catalyst may beinvestigated pursuant to the present invention, as well as knownheterogeneous catalysts for such reactions are shown in Table 1B. Thelibrary of candidate catalysts being screened can be variations in thestructure or composition of known catalysts or can be structurallyunrelated thereto. TABLE 1A Exemplary Homogeneous Catalytic ReactionsReaction Class Known Catalyst assymetric C-C double Ru-, Rh- ligand(e.g., phosphine) bond isomerization Suzuki biaryl cross- Pd-ligand(e.g., phosphine) coupling hydroformylation Co-, Rh- ligand (e.g.,phosphine, phosphite) hydrocarboxylation Mo-, Pd-, Rh-, Co-, ligand(e.g., phosphine) Heck reaction Pd-ligand (e.g., phosphine)hydrocyanation Ni-ligand (e.g., phosphite) assymetric hydrogenation Ru-,Rh- ligand (e.g., phosphine) Friedel-Crafts reaction HF, AlCl₃ olefinpolymerization Zr-, Ti-, Hf- ligand (e.g. cyclopentadiene) Ni-, Pd-ligand (e.g., N-, P- based) olefin metathesis Ru-, Mo- ligand (e.g., N-,P- based) methanol carbonylation Ir, Rh with halides (e.g., MeI, HI)epoxide ring opening Cu-ligand (e.g., alkoxide, amide, amine)

TABLE 1B Exemplary Heterogeneous Catalytic Reactions Reactant(s) ProductKnown Catalyst ethylene + vinyl acetate Pd-Au acetic acid ethyleneglycol glyoxal Cu ethylene ethyleneoxide Ag methanol formaldehyde Agbutene octene Ni dimerization HCl Cl2 Cu—Fe—Cl, Cu—Cr—O propyleneacrolein Bi—Mo—O acrolein acrylic acid Mo—V—O (+Cu—Mo—O+W—O)methacrolein methacrylic POM acid o-xylene Phthalic V/TiO2 anhydridebutane maleic VPO anhydride toluene benzonitrile V—Sb—O, Fe—Sb—Oethylbenzene styrene K—Fe—O (non-ODH) ethylbenzene styrene K—Bi—O/TiO2(ODH) propane propylene K—Cr—O/Al2O3 vinyl styrene Cu/zeolitecyclohexene cyclohexanol cyclohexanone Cu/SiO2 cyclohexene benzeneNM/support cyclohexylamine aniline NM/support side chain aromatic acidsCo—Mn—Zr-acetates aromatics ethylene acetaldehyde Pd—Cu, Pd—Auacetaldehyde acetic acid Mn-acetate propylene propylene oxideTi/silicalite butadiene vinyl oxirane Ag nitrobenzene aniline Cu/SiO2beta-picoline nicotinic acid V—Mo/Ti—Zr—O maleic gamma- anhydridebutyrolactone, tetrahydrofurane Cu—Zn—O, Cu—Cr—O propane acrylic acidV—Mo—Nb—O propane acryl nitrile benzene phenol Fe-Ga/zeolite syngasmethanol Cu—Zn/Al2O3 syngas methane Ni syngas fuel Fe, Co hydrocarbonsH2 + N2 ammonia Fe CH4 + H2O H2 + CO Ni DeNOx V/TiO2Supply of Candidate Materials to Microreactors

Two or more, and preferably four or more different candidate materialsbeing screened for their capability to enhance a chemical process aresupplied, preferably simultaneously, to a plurality of microreactors,such that each of the candidate materials is individually resident in aseparate microreactor. Specifically, a first candidate material issupplied to a first microreactor and, preferably simultaneouslytherewith, a second candidate material is supplied to a secondmicroreactor. If additional candidate materials are to be screened inadditional microreactors, then each additional candidate material ispreferably supplied simultaneously to respective individualmicroreactors, to form an array of microreactors, each of whichcomprises a candidate material to be screened. While the simultaneous,parallel loading of different candidate materials into the microreactorsis preferred, serial loading, including automated serial loading, of thecandidate materials may be appropriate for chemical processingMicrosystems having a moderate number of microreactors (e.g., not morethan about 100). In any case, particular candidate materials areconsidered to be different from other candidate materials if theycomprise different elements or compounds or compositions. Candidatematerials having the same composition can also be considered differentfrom each other if they have measurably different physical properties(e.g., thickness, crystalline structure, active surface area) orotherwise differ in form, and these differences impart differentprocess-enhancing activity (e.g., catalytic activity) to the twocandidate materials.

As noted, different candidate materials are loaded into separate,dedicated microreactors. Typically, however, not all of themicroreactors are supplied with a candidate material. As discussed belowin connection with the microreactors, some of the microreactors can,instead, comprise a control material. For example, one or more of themicroreactors can be supplied with a positive control (e.g., a knowncatalyst), left blank (without any additional candidate materialsupplied) or supplied with a negative control material.

Solid-phase candidate materials are preferably supplied to a pluralityof microreactors as an array of candidate materials. An array ofcandidate materials generally comprises a substrate and two or moredifferent candidate materials, and preferably four or more differentcandidate materials at separate portions of the substrate. The candidatematerials are spatially separated, preferably at an exposed surface ofthe substrate, such that the array of materials can be integrated withthe plurality of microreactors to include different candidate materialswithin different microreactors. Moreover, the different candidatematerials are also preferably separately addressable, for example, foranalytical characterization thereof. The two or more different candidatematerials are therefore preferably located at discrete, non-contiguous,individually addressable regions of the substrate, with the regionsbeing spaced to accommodate inclusion into a plurality of microreactors.The different candidate materials may, nonetheless, also be contiguouswith each other (e.g. as in a continuous gradient of different materialcompositions).

The substrate is any material having a rigid or semi-rigid surface onwhich the candidate material can be formed or deposited or to which thecandidate material can be linked.-The substrate can be of any suitablematerial, and preferably consists essentially of materials that areinert with respect to the chemical process of interest, and except wheredesired otherwise, with respect to the candidate materials beingscreened. Certain materials will, therefore, be less desirably employedas a substrate material for certain reaction process conditions (e.g.,high temperatures—especially temperatures greater than about 100° C.—orhigh pressures) and/or for certain reaction mechanisms. The substratematerial is also preferably selected for suitability in connection withmicrofabrication techniques, such as selective etching (e.g., chemicaletching in a liquid or gaseous phase, plasma-assisted etching, and otheretching techniques) photolithography, and other techniques known orlater-developed in the art. Silicon, including polycrystalline silicon,single-crystal silicon, sputtered silicon, and silica (SiO₂) in any ofits forms (quartz, glass, etc.) are preferred substrate materials. Otherknown materials (e.g., silicon nitride, silicon carbide, metal oxides(e.g., alumina), mixed metal oxides, metal halides (e.g., magnesiumchloride), minerals, zeolites, and ceramics) may also be suitable for asubstrate material. Organic and inorganic polymers may also be suitablyemployed in some applications of the invention.

As to form, the substrate can, but does not necessarily, have at leastone substantially flat, substantially planar surface, and is preferably,but not necessarily, a substantially planar substrate such as a wafer.The surface of the substrate can be divided into physically separateregions and can have, for example, dimples, wells, raised regions,etched trenches, or the like formed in the surface. In still otherembodiments, small beads or pellets may be the substrate, and such beadsor pellets may be included in an array, for example, for example,placing the beads within dimples, wells or within or upon other regionsof the substrate's surface. Frits can be used to hold such beads or.pellets in place. In yet another embodiment, the substrate can be aporous material. The substrate can, and is preferably, passive—having anessential absence of any active microcomponents such as valves, pumps,active heating elements, active mixing elements. The substrate alsopreferably has an essential absence of passive microcomponents such asmicrofluidic channels or apertures used for fluid distribution,heat-transfer elements, mass-transfer elements (e.g., membranes), etc.,or combinations thereof. In some embodiments, however, the substrate caninclude such active microcomponents or such passive microcomponents. Ina preferred embodiment, the substrate has a substantially flat uppersurface with a plurality of substantially coplanar indentations or wellsof sufficient depth to allow a quantity of candidate material to bedeposited, formed or contained therein. The overall size and/or shape ofthe substrate is not limiting to the invention. The size can be chosen,however, to be compatible with commercial availability, existingfabrication techniques (e.g., silicon wafer availability and/orfabrication), and/or analytical measurement techniques. Generally, thesubstrate will be sized to be portable by humans and/or to bemanipulated by automated substrate-handling devices. Hence, two inch andthree inch wafers are suitably employed. The choice of an appropriatesubstrate material and/or form for certain applications will be apparentto those of skill in the art based on the guidance provided herein.

The candidate material is preferably, in most cases, immobilized withrespect to the substrate, and once loaded into a microreactor, thecandidate material and/or the substrate are preferably immobilized withrespect to the microreactor. The immobilized material offers acontrolled geometry, such that fluid flow past, over, around or throughthe candidate material and/or the substrate will not vary theprocess-enhancing effect thereof during any particular experiment. Theconfiguration of the candidate material with respect to the substrateand/or the microreactor can be of any design which allows for one ormore reactants to contact the candidate material during the chemicalreaction or other chemical process. Hence, it can be appreciated thatthe exact configuration of the candidate materials and the substrate arenot limiting to the invention. Typical configurations, such as thosediscussed below, generally allow for flow past and around a candidatematerial formed on a surface of a reaction cavity, for unidirectionalflow of reactants through a porous substrate or through a bed of beads,or for flow of reactants into and out of a well comprising a porous ornon-porous substrate.

An exemplary embodiment of a chemical processing microsystem adapted foruse with an array of solid-phase candidate materials is shownschematically in FIG. 2. The array 100 comprises a substrate 110 havingone or more exposed surfaces 112 and having a plurality of candidatematerials 120 on the exposed surfaces 112 of the substrate 110, or onvarious portions thereof. The array can be integrally, and releasablypositioned between housing block 210 and reactor block 200, by bringingopposing surfaces 212 and 201 of the housing block 210 and reactor block200, respectively, into contact with each other, such that the array100, the exposed surface 112, and candidate material 120, taken togetherwith the plurality of wells 235 formed in the reactor block 200, definea plurality of microreactors. Each microreactor comprises a surfacedefining a reaction cavity and at least a portion of amaterial-containing region of the substrate 110 within the reactioncavity. Reactants can be supplied to the microreactors through inletports 250 (260), and the reactor effluent can be discharged from themicroreactors through outlet ports 260 (250). A seal such as a gasket300 having a plurality of apertures arranged to correspond with thearrangement of the plurality of wells 235 and of the arrangement ofcandidate materials 120 may be situated between the array 100 and thereactor block 200 to independently seal each microreactor once thehousing block 210 and reactor block 200 are brought together. Thehousing block 210 and reactor block 200 may be brought into contact witheach other (to engage the array 100) through parallelthreaded-connectors 215 (e.g., bolts), through hydraulic means, throughspring-pressure or through other suitable compressive-force fastener.Engaging and/or releasing the array of materials 100 from themicroreactors 600, and specifically, from the housing block 210 andreactor block 200, may be effected as a manual or an automatedoperation.

The array of materials preferably comprises one or more films-at anexposed surface of the substrate. The film can have an average thicknessranging from about 0.01 Wun to about 100 μm, and more preferably rangingfrom about 0.05 μm to about 10 μm, and most preferably from about 0.1 μmto about 1 μm. With reference to FIG. 3, a film can be formed on theexposed surface of the substrate—with different materials at differentdiscrete regions thereof (e.g., FIG. 3A), or with different materialscontiguous to each other (e.g., FIG. 3B). In alternative configurations,the exposed surface of a given film can be (1) in a plane that issubstantially parallel to, and external to (that is, elevated relativeto) the exposed substrate surface 112 (e.g., FIG. 3A, FIG. 3B), (2)substantially coplanar with the exposed substrate surface 112 (e.g.,FIG. 3C) or (3) in a plane that is substantially parallel to, andinternal to (that is, depressed relative to) the exposed substratesurface 112 (e.g., FIG. 3D). For correlation purposes (with FIG. 2, forexample), the exposed substrate surface 112 on which the film residesmay or may not be the same surface as the upper-most surface 102 of thematerial-containing array 100.

A film of a material can be formed, for example, by depositing thematerial or material precursors (e.g., individual components of acomposition) onto an exposed surface of the substrate, and whereappropriate, treating to react the deposited material precursors witheach other. Such post-deposition treatment can be completed before orafter loading the candidate materials into the microreactors. Suitablemethods for depositing a film of materials include physical vapordeposition (e.g., evaporation, sputtering, ion plating), chemical vapordeposition, plasma-assisted chemical vapor deposition,electrodeposition, electrochemical deposition, coating techniques (e.g.,spray drying, spray coating, pyrolysis), and solution-based techniques(e.g., sol-gel, impregnation, precipitation), among others. The film canalso be formed by in situ growth at a substrate surface, by diffusion ofthe material into a substrate surface, or by conversion of the substratematerial (e.g., thermal oxidation ). Such approaches and others arediscussed in detail in Bunshah, Handbook of Deposition Technologies forFilms and Coatings, 2^(nd) Ed., Noyes Publications (1994), andreferences cited therein. The candidate materials may be applied indiscrete, individually addressable regions l0 using mechanical orchemical masking approaches. For example, mechanical masks or shutterscan be used in connection with many of the aforementioned depositiontechniques to create an array of films in a desired arrangement.Distinct regions of candidate materials may also be formed usingfilm-formation approaches that are or can be controlled to beregion-selective—without masking. Spray drying and electrochemicaldeposition approaches are exemplary region-selective approaches.Different candidate materials may alternatively be applied contiguous toeach other. The array can comprise, for example, a contiguouscomposition gradient of two or more components. Contiguous naturalcomposition gradients can be formed, for example, by multiple-targetvapor deposition approaches. See, e.g., Hanak et al., OptimizationStudies of Materials in Hydrogenated Amorphous Silicon Solar Cells,Photovoltaic Solar Energy Conference, Berlin (1979), and van Dover etal., Discovery of a Useful Thin-Film Dielectric Using aComposition-Spread Approach, Nature, Vol. 392, No. 12, pp. 162-164(1998). Contiguous controlled gradients can be formed, for example, byorchestrated (e.g., programmed) masking or shuttering approaches withmulti-target deposition, such as those disclosed in copending U.S.patent application Ser. No. 09/237,502 filed Jan. 26, 1999 by Wang etal.

Preferred approaches for forming an array of candidate materials includevapor deposition techniques disclosed in U.S. Pat. No. 5,776,359 toSchultz et al., sol-gel solution-based techniques disclosed incommonly-owned co-pending U.S. patent application Ser. No. 09/156,827,filed Jan. 18, 1998 by Giaquinta et al., electrochemical depositiontechniques disclosed in commonly-owned co-pending U.S. patentapplication Ser. No. 09/119,187, filed Jul. 20, 1998 by Warren et al.,and in situ impregnation techniques for creating arrays of supportedcatalysts as disclosed in commonly-owned co-pending U.S. patentapplication Ser. No. ______, filed Mar. 1, 2000 by Lugmair et al., eachof which is incorporated by reference for all purposes. Thecombinatorial library embodied in the array of candidate materials ispreferably designed with the assistance of library design software suchas LIBRARY STUDIO™ software (Symyx Technologies, Inc., Santa Clara,Calif.). Preparation of the arrays can be advantageously effected usingautomated liquid handling robots (e.g., CAVRO Scientific Instruments,Inc.), under control of software such as IMPRESSIONIST™ software (SymyxTechnologies, Inc.).

The amount of an individual candidate material deposited as a film (orotherwise included) on a particular portion of the array is not limitingto the invention. The required amount will vary depending upon therequired surface area of the film and the required thickness of thefilm, each of which will, in turn, vary depending upon the chemicalprocess of interest, the geometry of the microreactor, and the requiredresidence time or contact time of reactants in the microreactor, amongother factors. In general, the amount of an individual candidatematerial is typically not more than about 25 mg, preferably not morethan about 10 mg, and can be not more than about 7 mg, not more thanabout 5 mg, not more than about 3 mg and not more than about 1 mg. Inpreferred embodiments, the amount of an individual candidate materialcan range from about 0.1 μg to about 100 mg, preferably from about 1 μgto about 10 mg, more preferably from about 10 μg to about 10 mg and mostpreferably from about 100 μg to about 1 mg.

While an array of one or more films is advantageously employed inconnection with the present invention, other array configurations canalso be employed to supply the two or more solid-phase candidatematerials to a plurality of microreactors. The array can comprise, forexample, the candidate materials loaded into the microreactors in bulkform, or as bonded to or linked to porous materials or tomicroparticles. With reference again to FIG. 3, the array can comprise,for example, a substrate 110 having a plurality of wells 130 formed inan exposed surface 112 of the substrate (e.g., FIG. 3E, FIG. 3G) orhaving a plurality of apertures 140 extending between first and secondsubstantially parallel surfaces 111, 112 of the substrate 110 (e.g.,FIG. 3F, FIG. 3H). Such a well 130 or an aperture 140 can comprise aporous material 122 (e.g., FIG. 3E, FIG. 3F) to which a particularcandidate material is bonded, preferably covalently bonded. Exemplaryporous materials include quartz, glass or alumina, etched microchannelsor glass plates, diatomaceous earth, etc. As another alternative, a well130 or an aperture 140 can comprise microparticles 124, typicallyreferred to in the art as “latex particles” or “beads”, to which aparticular candidate material is bonded, and preferably covalentlybonded (FIG. 3G, FIG. 3H) or, alternatively, bulk candidate materials124′ (FIG. 3G, FIG. 3H). The beads can be held within the well 130 oraperture 140 by frits 126. Exemplary microparticles include polystyreneparticles, controlled pore glass (CPG), etc.

Liquid and/or gaseous phase candidate materials may also be supplied tothe plurality of microreactors in an array format. For liquids, an arrayof wells with different liquid candidate materials in each well can beemployed. For gasses, an array of different time-release materials thatrelease the candidate gas of interest over time can be employed.Alternatively, either liquids (e.g., soluble candidate materials) orgasses can be adsorbed onto inorganic or organic substrates to form a“solid-phase” form thereof (e.g., as a useful heterogeneous catalyst).It may be preferable, however, to supply different candidate liquidand/or gaseous phase candidate materials to the plurality ofmicroreactors using a fluid distribution manifold, as described below inconnection with the supply of reactants to the plurality ofmicroreactors.

The number of candidate materials to be screened in any cycle ofscreening is not narrowly critical, and can range, for example, from twoto about a million, and even more, ultimately depending on the number ofmicroreactors available for the screening. More specifically, the numberof different candidate materials to be supplied to differentmicroreactors is at least 2, preferably at least 5, more preferably atleast 10, still more preferably at least 25, even more preferably atleast 50, yet more preferably at least 100, and most preferably at least250. Present microscale and nanoscale fabrication techniques can beused, however, to prepare arrays having an even greater number ofdifferent candidate materials. For higher throughput operations, forexample, the number of different candidate materials can be at leastabout 1000, more preferably at least about 10,000, even more preferablyat least about 100,000, and most preferably at least about 1,000,000 ormore. The fabrication of arrays comprising very large numbers ofdifferent candidate materials is enabled by fabrication techniques knownin the integrated circuit arts. See, for example, S.M. Sze,Semiconductor Sensors, Chap. 2, pp.17-96, John Wiley & Sons, Inc.(1994). Such approaches have been adapted in other aspects of catalystresearch. See, for example, Johansson et al., Nanofabrication of ModelCatalysts and Simulations of their Reaction Kinetics, J. Vac. Sci.Technol., 17:1 (January/February 1999).

If the two or more candidate materials are to be deposited on distinct,individually addressable regions of the substrate, the separationbetween adjacent regions can range from about to about 50 μm to about 1cm, more preferably from about 100 μm to about 7 mm, and most preferablyfrom about 1 mm to about 5 mm. The inter-region spacings can be not morethan about 1 cm, not more than about 7 mm, not more than about 5 mm, notmore than about 4 mm, not more than about 2 mm, not more 1 mm, not morethan about 100 μm, and not more than about 50 μm. Exemplaryinter-regions spacings (center-to-center) based on preferred embodimentsof the invention are 4 mm for having 256 addressable regions on athree-inch wafer substrate, and 2 mm for having 1024 addressable regionson a three-inch wafer substrate. As such, the surface density ofdiscrete candidate material regions can range from about 1 region/cm² toabout 200 regions/cm², more preferably from about 5 regions/cm² to about100 regions/cm², and most preferably from about 10 regions/cm² to about50 regions/cm². The planar density can be at least 1 region/cm², atleast 5 regions/cm², at least 10 regions/cm², at least 25 regions/cm²,at 50 regions/cm², at least 100 regions/cm², and at least 200regions/cm². For some reactions, lower or mid-range densities may bepreferred. For other reactions, higher densities may be suitable.Additionally, even higher densities may be achieved as fabricationtechnology develops to nano-scale applications. As discussed below, thearrangement of the plurality of candidate materials (includingseparation and relative spatial address) and the plurality of regionsshould be correlated with the arrangement of microreactors forintegration therewith.

In a preferred embodiment, the array of candidate material consists of,or alternatively, consists essentially of, the substrate and two or moredifferent materials at separate portions of the substrate. As used inthis context, the phrase “consists essentially of is intended to excludeother microcomponents such as valves, active mixers, fluid distributionmanifolds, etc, without excluding structure whose function is merely tohold a candidate material in a particular position or to confine acandidate material to a particular space. For example, embodiments thatinclude microparticles and frits, if they do not contain othermicrocomponents such as distribution channels, valves, etc., are stillconsidered to “consist essentially of” the candidate material ofinterest and the substrate, since the frits and microparticles serveonly to confine the candidate material between the frits. The separateportions can be contiguous to each other, or separated by substratematerial or other (e.g., insulating) material. Separated regions may bepreferred if substantial interdiffusion between contiguous candidatematerials is likely and may present erroneous data. The separateportions can be at or above a surface of the substrate or within a wellor aperture provided in the substrate.

With reference again to FIG. 1C, a distinct advantage of supplying theplurality of candidate materials as a modular material array 100 is thatan entire libraries of candidate materials can be efficiently loaded tothe plurality of microreactors, screened therein, and then unloadedtherefrom. The microreactors can subsequently be reloaded with otherlibraries. Hence, in a preferred embodiment, the array of candidatematerials is interchangeable with the microreactor mother structurewithout affecting the structural integrity of other systemmicrocomponents. For example, the array of candidate materials ispreferably independent of the structural integrity of each of thefollowing systems (considered independently or collectively): a fluiddistribution system, a heat-transfer system, an analytical system, and amixing system. A plurality of material arrays 100, 100′, 100″ (FIG. 1C)can be transferred to and/or from the chemical processing microsystem 10using a material library handling system 5 (FIG. 1C). Such transfer canoccur manually (e.g., by hand), semiautomatically (e.g., using ahuman-controlled robotics) or automatically (e.g., using mechanical,hydraulic, pneumatic, robotic or other automated means). Exemplarysystems include wafer-handling equipment known in the integrated-circuitmanufacturing arts.

A number of variations can be employed with respect to the geometry withwhich the array of candidate materials is interchangeably integratedwith the microreactors. Several exemplary geometries are shown in FIGS.4 and 5. Each of FIGS. 4A through 4E and FIG. 5 show an individualmicroreactor as a cut-away view from an array of microreactors. Each ofthe microreactors of FIGS. 4A through 4E, and FIG. 5 are formed in aplurality of adjacent laminae, with at least one of the laminae being amaterial-containing array laminate 100, and a reactor block 200comprising one (e.g., FIG. 4A through 4E, FIG. 5) or more (e.g., FIG.4C) laminae and having a well 235 (e.g., FIG. 4A, FIG. 4C, FIG. 4D, FIG.4E, FIG. 5) or an aperture 240 (FIG. 4B). As shown in FIG. 4C, awell-type structure can be formed in a composite reactor block 200 fromtwo adjacent laminae 220, 230 by combining a reactor laminate 220 havingan aperture 240 with a capping laminate 230. One or more of thematerial-containing laminates 100, taken together with the reactor block200 (or optionally, with laminates 220 and 230), form a microreactorhaving an interior surface that defines a reaction cavity. Each of themicroreactors shown in FIGS. 4A through 4E and FIG. 5 also comprise oneor more inlet ports 250 in fluid communication with the reaction cavityfor supplying one or more reactants (or co-reactant candidate material)thereto, and preferably, one or more outlet ports 260 in fluidcommunication with the reaction cavity for discharging one or morereactant products or unreacted (e.g., excess) reactants therefrom.

The material-containing laminate 100 will preferably form a portion ofthe reaction-cavity-defining surface of the microreactor. For example,with reference to FIGS. 4A through 4D, the material-containing laminate100 comprises a candidate material 120 at an exposed surface 112 of asubstrate 110. FIG. 4A shows a microreactor geometry with a singlereaction cavity defined by a well-containing reactor block 200 and asingle material-containing laminate 100. FIG. 4B shows a microreactorgeometry with a single reaction cavity defined by an aperture-containingreactor block 200 and two material-containing laminates 100. Thismicroreactor geometry provides an increased surface area of thecandidate material, or alternatively, allows for supplying two differentmaterials to the same microreactor. FIG. 4C shows a microreactorgeometry with two independent reaction cavities, each reaction cavitybeing defined, in part, by a common material-containing laminate 100.The two independent reaction cavities can be isolated from each other(e.g., by using separate fluid distribution systems for each reactioncavity), or can be in fluid communication with each other (e.g., bycross-connecting the fluid distribution systems, such that the outletfrom a first cavity is in fluid communication with an inlet to thesecond cavity). The geometry of FIG. 4C provides for efficient use ofcandidate material arrays, and increases the microreactor density of thechemical processing microsystem. FIG. 4D shows a microreactor geometrywith a single reaction cavity defined by two well-containing reactorblocks 200, 200′ and by an annular surface 112 defining an aperture inthe substrate 110, with the film of candidate material 120 being formedon a part of the annular surface 112.

The material-containing laminate 100 can, however, be integral with themicroreactor without forming a substantial portion of thereaction-cavity-defining surface thereof. In the microreactor geometryshown in FIG. 4E, for example, the material containing laminate 100comprises microparticles 124, to which candidate material 120 is bonded,held in place between frits 126. Because a fluid-phase reactant can flowpast the candidate materials and through the material-containinglaminate, (for example, from well 235 to well 235′), such laminate doesnot define a substantial portion of the boundary surface of the reactioncavity.

The candidate materials-are preferably, but not necessarily, arranged onthe substrate in a substantially co-planar relationship with each other.While the plurality of candidate materials on an array, and theplurality of microreactors formed in a plurality of laminae arepreferably coplanar with each other, alternative, non-planar geometriescan, nonetheless, also be employed. For example, FIG. 5 shows aplurality of non-planar microreactors formed in a plurality of laminae.

In a preferred embodiment, an array of solid candidate materials, suchas prospective heterogeneous catalysts, are deposited by sol-geltechniques or in situ * impregnation techniques onto a substantiallyplanar substrate having a plurality of S substantially co-planar wellsformed at one surface of the substrate. With reference to FIGS. 6A and6B, a silicon dioxide (quartz or glass) substrate 110 can comprise 256circular-shaped wells 130 arranged in a sixteen-well-by sixteen-wellsquare array, with each well having a diameter of about 1.25 mm and adepth of about 0.05 mm. The distance between wells is about 4 mm. Thepreferred well-containing substrate 110 can be formed, for example, bymasking a glass or quartz wafer with polycrystalline silicon usingphotolithography techniques, and then etching with a suitable etchant,such as hydrofluoric acid (HF), or alternatively, by mechanical means(e.g., machining, grinding, or bead-blasting). Candidate materials canthen be deposited by sol-gel techniques or in situ impregnationtechniques, such as those referred to above, to form thematerial-containing array 100. In an alternatively preferred embodiment,the material array comprises up to 1024 candidate materials on asubstrate having 1024 wells arranged in a 32-well by 32-well squarearray. Such a material array can be prepared, for example, as describedabove in connection with the 256-well array, except that the distancebetween wells is reduced to about 2 mm.

As noted, a primary advantage of including the candidate materials on anarray of materials is that the plurality of candidate materials can beloaded to (and subsequently unloaded from) the plurality ofmicroreactors in parallel—by incorporating (or withdrawing) the entirearray. In an alternative embodiment, the plurality of candidatematerials could be serially loaded into an array (or directly into aplurality of microreactors). For such serial-loading approaches, thecandidate materials may be encapsulated or otherwise prepared forhandling and insertion into the microreactors.

Supplying Reactants to the Microreactors

With reference to FIG. 1C, reactants can be supplied to the plurality ofmicroreactors 600 from an external distribution system 480 comprisingone or more reactant sources. The external fluid distribution system 480can comprise, for example, gaseous reactant sources 482 (e.g., gascylinders), a gas flow-control device 483 (e.g., a mass-flow controller(MFC)), one or more control valves 484, preferably operated by acontroller 485, and a common supply line 486 drawn from a mixing zone487. The valves 484 and mixing zone(s) 487 can be housed within an oven489. Liquid reagent sources 490 can likewise be supplied through aliquid-flow-control device 491 (e.g., syringe pumps; HPLC pumps). Liquidreactants can, if desired, be vaporized and provided to themicroreactors in a vaporous state using methods and devices known in theart. According to one approach, the vapor in the head space over atemperature-controlled liquid can be provided to a mass flow controller(optionally heated) or other gas flow-control device. Alternatively, gasmetered through an MFC can be bubbled through a temperature-controlledliquid. Other methods known or later developed for liquid delivery canalso be employed.

A microfluidic distribution system can provide fluid communicationbetween the external fluid distribution system 480 and each of theplurality of microreactors 600 (e.g., through one or more common inletports 510 to the chemical processing microsystem 10). With reference toFIG. 2, for example, distribution manifold 500 can provide fluidcommunication between the microreactors 600 and an external fluiddistribution system 480 (through common inlet port 510 and reactor inletport 250). Fluid communication between each of the microreactors and theexternal distribution system 480 can also be provided for reactoreffluent (e.g., through reactor outlet ports 260), as discussed below.

Another exemplary reactant supply (or discharge) manifold is depictedschematically in FIG. 7A. The supply manifold 500 comprises a singlecommon inlet port 510, and a plurality of terminal outlet ports 520. Theterminal outlet ports 520 are in fluid communication with the commoninlet port via a common header 512 and a plurality of channels 514oriented approximately normal to the common header 512.

For applications directed toward identifying new materials, thereactants are preferably supplied to the plurality of microreactors suchthat the inlet pressure of the fluid at each microreactor and theflow-rate (mass/volumetric flow rate) through each microreactor aresubstantially the same for each of the plurality of microreactors—toallow a basis for comparing different candidate materials. As such, thereactant supply manifold depicted in FIG. 7A, while adequate for someapplications (e.g., with less than ten microreactors), is a lesspreferred embodiment. Because the pressure drop along the common header512, varies over the distance, “L”, the pressure at each terminal outletport (and therefore, at each microreactor inlet) will vary, and the flowrate through each microreactor will vary. While the difference inpressures could be minimized by increasing the distance, “d”, of thecommon header 512 such that the pressure at any distance, L, isapproximately the same, the space constraints imposed by such anapproach make such a design less desirable with more than about 10microreactors.

A preferred fluid distribution manifold is, therefore, designed to suchthat the flow paths to each of the microreactors have equalconductance—for example, flow paths of equal length and equivalentgeometry—from the common port to each of the terminal ports. Withreference to FIG. 7B, a preferred embodiment for a distribution manifold500 comprising flow paths to a plurality of microreactors 600 cancomprise a common port 510 adaptable for fluid communication with one ormore reactant sources through one or more supply or recovery headers ofan external fluid distribution system, 2^(n) terminal ports 520adaptable for fluid delivery to or fluid recovery from 2^(n)microreactors (or, in the general case, other microcomponents), and adistribution channel (generally indicated as 514) providing fluidcommunication between the common port 510 and each of the 2^(n) terminalports 520. To provide flow paths of equal length and equivalentgeometry, the distribution channel 514 can comprise 2^(n)-1 channelsections 515, 516, 517 connected with each other through 2^(n)-1 binaryjunctions 518. Each of the 2^(n)-1 channel sections 515, 516, 517 has atleast three access ports serving one or more of the following functions:as a common port 510; as a connection port for a binary junction 518; oras a terminal port 520. Specifically, a first channel section 515 hasaccess ports serving as the common port 510 and as connection ports fortwo binary junctions 518. Additionally, [2^(n-1)-2] intermediate channelsections 516 have access ports serving as connection ports for threebinary junctions 518. Moreover, [2^(n-1)] terminal channel sections 517have access ports serving as a connection port for one binary junction518 and as two terminal ports 520.

To ensure equal flow-path lengths and substantially equivalent flowgeometry, each of the channel sections 515, 516, 517 are preferablylinear and the three access ports for a given channel section arepreferably symmetrically arranged with one access port at the center ofthe linear channel section and one access port at each of the two endsof the linear channel section. Moreover, the linear channel sections arepreferably configured to be mutually orthogonal to each other (formingright angles with each other at each binary junction). The channelsections may, however, be non-linear, include elbows (e.g., channelsection 515), and/or be non-orthogonally oriented as long as the binarysymmetry is preserved. The common port 510, channel sections 515, 516,517, binary junctions 518 and terminal ports 520 are each preferablyarranged in a common plane. For more complex designs, however, some ofthe components could be arranged in a non-planar, three-dimensionalconfiguration.

As shown in FIG. 7B, each of two fluid distribution manifolds 500provide fluid communication between a common port 510 and 128microreactors 600, thereby serving a total of 256 microreactors. Hence,for each of the two fluid supply manifolds of FIG. 7B, the number, “n”is 7. In general, however, n, can be an integer not less than 4, andpreferably ranges from about 4 to 20. The number, n, is more preferablynot less than 6, even more preferably not less than 8, still morepreferably not less than 10, and most preferably not less than 12. Thenumber, n, can more preferably range from 6 to 18, even more preferablyfrom 8 to 16, and most preferably from 8 to 12. Table 2 shows thedetails for a binary-tree fluid distribution manifold where n rangesfrom 4 to 8. Specifically, Table 2 shows the number of microcomponentsto which a fluid can be communicated, the number of binary junctionsassociated therewith, and the number of channel sections associatedtherewith. TABLE 2 Binary-Tree Distribution Manifold Number (#) ofChannel Sections # of Terminal Sections Terminal # of Binary 1^(st)Channel Section Intermediate Sections (w/1 binary junction Ports servedJunctions Total # (w/common port and 2 (w/3 binary junctions) and 2terminal ports) n (2^(n)) (2^(n) − 1) (2^(n) − 1) binary junctions)(2^(n−1) − 2) (2^(n−1)) 4 16 15 15 1 6 8 5 32 31 31 1 14 16 6 64 63 63 130 32 7 128 127 127 1 62 64 8 256 255 255 1 126 128

Advantageously, the preferred, binary-tree distribution system allowsfor very efficient, uniform distribution of microcomponents intwo-dimensional space, and thereby enables a higher microcomponentplanar density—for example, a planar density of at least 1microcomponent/cm², and preferably at least 5 microcomponents/cm². Suchan approach is particularly advantageous when incorporated into modular,laminae-type systems such as the preferred embodiment disclosed herein,because it allows for modular interchangeability of microcomponentdistribution system without affecting the structural integrity of othersubsystems.

The concept of the binary-tree distribution manifold shown in FIG. 7Bcan likewise be extended to higher order distribution manifolds. Forexample, a ternary-tree design can comprise a common port adaptable forfluid communication with one or more supply or recovery headers, 3^(n)terminal ports adaptable for fluid delivery to or fluid recovery from3^(n) microcomponents, and a distribution channel providing fluidcommunication between the common port and each of the 3^(n) terminalports. To provide flow paths of equal length and equivalent geometry forternary or even higher-order manifolds, however, the distributionchannels thereof are preferably arranged in three-dimensions, andpreferably on substantially parallel planar surfaces (e.g., wafers) withthe ternary (or higher order) junctions at each level of distributionbeing co-planar with each other. The number of planar surfaces will beequal to the number “n”. The concept of such a higher order distributionsystems are illustrated in FIGS. 7C and 7D for ternary and quaternarydistribution systems, respectively, for the case where n=3. Thequaternary-tree distribution system of FIG. 7D is preferred over theternary system with respect to maximizing device density.

Regardless of the design of the distribution manifold, the shape and/ordimensions the distribution channel are not limiting, except asspecifically recited in the claims. The cross-sectional shape of achannel can be, for example, approximately square, rectangular,circular, oval, etc., or even irregular in shape, and may be determinedprimarily by the fabrication techniques employed. Approximately squareor rectangular channels are typical, and the aspect ratio (width/depth)can be greater than 1, equal to 1 or less than 1. See, for example, U.S.Pat. No. 5,842,787 to Kopf-Sill et al. Because, however, the shapeand/or dimensions of the distribution channel will affect the flow rateof reactants through each microreactor, these factors should beconsidered in connection with the overall chemical processingmicrosystem design, as discussed below in connection with themicroreactor design. In general, the distribution channel can havedimensions, for an approximately square cross-section, of not more thanabout 1 cm×1 cm, preferably of not more than about 5 mm×5 mm, morepreferably not more than about 2 mm×2 mm, even more preferably of notmore than about 1 mm×1 mm, and still more preferably of not more thanabout 100 μm×100 μm. Smaller dimensions can also be suitably employed insome applications, including dimensions of not more than about 10 μm×10μm, not more than about 1 μm×1 μm, and not more than about 0.5 μm×0.5μm. The channel can have a rectangular cross-section with an aspectratio of greater or less than one, and dimensions adjusted to as toprovide the same general ranges of cross-sectional flow area asdescribed for a square cross-sectional channel. For an approximatelycircular cross-section, the diameter can be not more than about 1 cm,preferably not more than about 5 mm, more preferably not more than about2 mm, even more preferably not more than about 1 mm, and still morepreferably not more than about 100 μm. Smaller dimensions can also besuitably employed in some applications, including a diameter of not morethan about 10 μm, not more than about 1 μm, and not more than about 0.5μm. Described in terms of hydraulic radius, the distribution channel canhave a hydraulic radius of not more than about 2.5 mm, more preferablynot more than about 1.25 mm, even more preferably of not more than about0.5 mm, yet more preferably of not more than about 0.25 mm, and mostpreferably not more than about 25 μm. Smaller hydraulic radii can alsobe suitably employed in some applications, including a hydraulic radiusof not more than about 2.5 μm, not more than about 0.25 μm, and not morethan about 0.125 μm. Hence, the hydraulic radius of the distributionchannel preferably ranges from about 2.5 mm to about 0.125 μm, morepreferably from about 1.25 mm to about 0.25 μm, and most preferably fromabout 2 mm to about 2.5 μm.

The shape and dimensions of the cross-section of the distributionchannel can be constant along the entire length of a distribution pathor, if desired, can be varied along such length. If shape and/ordimensions of the channel are varied along the fluid-distribution path,however, the binary (or ternary, quaternary, etc.) symmetry is, in someapplications, preferably maintained to provide for equal conductancealong each fluid-distribution path. In other applications, theconductance of each flow path can be purposefully varied to provide fora tailored flow distribution to the plurality of microreactors (andcorresponding tailored residence times, etc).

The distribution manifold can preferably provide, in addition to itsfluid-distribution function, a pressure reducing function. The pressurereducing function can be in the supply manifold or, if desired, in thedischarge manifold. In general, the biggest pressure drop in the systemis designed to be outside of the microreactor, to minimize the effect ofminor variations in microreactor fabrication or catalyst loading onreactor pressure. Moreover, the biggest pressure drop is preferablydesigned to occur in the supply manifold, immediately before eachmicroreactor. Such a design minimizes the cross-microreactor effect inthe event that flow through one of the microreactors becomes inoperative(e.g., blocked or clogged). Pressure reduction can be achieved throughactive microcomponents (e.g., microvalves) or passive microcomponents(e.g., microscale flow restrictors). Pressure reduction can also be, andis preferably, achieved by reducing the cross-sectional flow area (andtherefore, the hydraulic radius) of the distribution channel along thelength thereof. For the preferred binary-tree embodiment, for example,the cross-sectional flow area of each channel section can be reduced ateach binary junction relative to the immediately preceding (upstream)channel section. Most preferably, the cross-sectional flow area isreduced by ½ at each binary junction, thereby resulting in asubstantially linear pressure drop along the flow-path from the commonport to the terminal port.

The length of the distribution path between the common port and eachterminal port is not generally limiting. In preferred embodiments,however, the length of each of the flow paths is designed such that theconductance is substantially the same for each of the flow paths. In asubstantially planar binary-tree design, such as that shown in FIG. 7B,the overall length of each flow path, L, will generally depend on thearrangement of the microcomponents 600 and on the inter-component space.

The distribution manifolds of FIGS. 7B and 7I are preferred fluid-supplymanifolds suitable for use in connection with the preferred array ofcandidate materials depicted in FIG. 6A and discussed in connectiontherewith. Referring to FIG. 7B, the common port 510 has a circularcross-sectional shape and an inside diameter of about 2 mm feeding intoan associated short common header 512 having an approximatelyrectangular cross-section with a width of 2 mm and a depth of about 20μm. Two L-shaped first channel sections 515 (that feed the first twochannel sections having three binary junctions) have a generallyrectangular cross-sectional with a first leg of the L-shaped firstchannel section 515 having a width of about 2 mm, and the second leg ofthe L-shaped first channel section 515 having a width of about 1 mm, andin each case, a depth of about 20 μm. The width of each successiveintermediate channel sections 516 (having three binary junctions) isthen reduced by ½ relative to the preceding intermediate channelsection, with the depth thereof remaining at about 20 μm. FIG. 7E is aschematic of a one flow path of the distribution manifold of FIG. 7B,and shows a portion of the first channel section 515, severalintermediate channel sections 516 and terminal channel sections 517 influid communication with several microreactors 600. As shown therein,the width of each successive intermediate channel section 516 is reducedby a factor of about ½, and the terminal channel section has a width ofabout 10 μm and a depth of about 10 μm. The overall length of the flowpath from the common port 510 to each of the 128 terminal ports 520 isabout 60 mm. FIG. 7F shows an enlarged top plan view of a microreactor600 in fluid communication with a terminal channel section 517 throughterminal port 520 of the distribution channel (which also serves asinlet port 250 of the microreactor 600). A microreactor outlet port 260is also shown—located at the top of the microreactor 600 (as shown inFIG. 8 and discussed in connection therewith).

The preferred distribution manifold of FIG. 7B can be interfaced with anexternal fluid distribution system 480 (FIG. 1C) by a number ofdifferent approaches. In a preferred approach, with reference to FIG.7B, vertical conduits (not shown in FIG. 7B) can extend normal to theplane of the binary-tree distribution system and connect to common inletports 510. (See FIGS. 18G and 18H and discussions in connectiontherewith). While shown in FIG. 7B as two common inlet ports 510 locatednear the edges of the wafer, a single, centrally-located common inletport (shown with dashed circle as 510′) could likewise be employed, andconnected the binary tree of FIG. 7B through an alternative firstchannel section (shown with dashed lines as 515′) and through anintermediate channel section (shown with dashed lines as 516′). As shownin FIG. 7I, a single common inlet port 510 can alternatively be locatednear the peripheral edge of the wafer.

In the general case, a binary-tree, regular square array of M×Mmicrocomponents (such as microreactors) can be designed according to thefollowing approach. Preferably, the following design parameters aredetermined in advance—based on system requirements for which the fluiddistribution manifold will be designed: the number of microcomponents(e.g., expressed as a binary exponential, 2^(n)=M²); an inter-componentspacing, Δl; the volumetric flow rate, V_(terminal), (or mass flow rate,m); the outlet pressure, p_(terminal), required at each terminal port;the inlet pressure, p_(common), required at the common port; and achannel cross-sectional geometry. The overall length, L, for each of theflow paths can be calculated from the number of microcomponents and theinter-component spacing by the following Equation 1:L=Δl(2^(2/n-)1)   Equation 1Then, the channel dimensions for the give channel geometry can bedetermined, based on conductance, to provide the desired pressure dropfor the desired flowrate. For example, the necessary channel height fora channel of length L having an approximately rectangularcross-sectional dimensions of h×w can be calculated by Equation 2:h=[24(μLQ)(l/w)(p _(common) ² −p _(terminal) ²)⁻¹]^(1/3)   Equation 2where μ is the fluid viscosity and Q is the pressure-volume per unittime.

The aforedescribed binary-tree, ternary-tree or quaternary-treedistribution manifolds can be employed as a microfluidic supply manifoldor as a microfluidic discharge manifold for any application requiringthe supply of fluids from a common port to a plurality ofmicrocomponents. In preferred applications, the distribution manifoldcan supply reactants, non-reacting fluids (e.g., carriers), and/orcandidate materials to the plurality of microreactors. In otherapplications, for example, the distribution manifold could also beemployed for high-precision parallel dispensing of a fluid to aplurality of microcontainers (for example, for dilution, scavenging,purging, etc.).

An alternative fluid distribution system design is shown in FIG. 7G.With reference thereto, distribution manifold 500 comprises fluid-supplyflow paths to an array of thirty-two microreactors 600. Fluidcommunication between common port 510 and microreactors 600 is providedthrough common headers 512 and supply channels 514. As depicted, each ofthe supply channels 514 have substantially the same flow-path length andequivalent geometry, thereby having equal conductance, and providingsubstantially the same pressure and flow rate at each of themicroreactors 600.

The distribution manifold (for both supply and/or effluent) is, in anycase, preferably a modular component, such as a wafer, and preferably inreleasable and/or sealed contact with other components of themicroreactor structure, such that different distribution manifolds canbe readily interchanged with each other. Such a design provides a meansfor changing the reaction conditions (e.g., flow rate, residence time)for a plurality of microreactors by a simple exchange of the modulardistribution wafer.

While the aforedescribed fluid distribution manifold is a preferredembodiment of the invention, other parallel-fluid distribution schemesmay also be employed. In general, for parallel fluid distributionsystems, the ratio of distribution manifold terminal outlet ports (i.e.,corresponding to microcomponent inlet ports) to distribution manifoldcommon inlet ports is preferably at least 10:1, more preferably at least20:1, and can, for higher number of microcomponents, be at least 30:1,at least 50:1, at least 75:1, at least 100:1, at least 150:1, at least200:1 and at least 250:1 or higher. Instead of simultaneous, paralleldelivery, however, rapid-serial delivery of fluids to each of themicroreactors may also be employed. Serial-parallel hybrid deliverysystems, involving rapid successive parallel delivery of fluids to asubset of the total number reactors may likewise be effective with thepresent invention. Such a rapid-serial-parallel approach is described,for example, in copending U.S. patent application Ser. No. 09/093,870,filed Jun. 9, 1998 by Guan et al.

Microreactors

The particular design of the microreactors employed in connection withthe present invention is not limiting, except as specifically recited inthe claims. The microreactor design can vary, for example, depending onthe type of chemical process being investigated, and with respect tochemical reactions, depending on the particular reaction being effected.Generally, for chemical reactions, each of the plurality ofmicroreactors in a chemical processing microsystem comprises a surfacedefining a reaction cavity for carrying out a chemical reaction, aninlet port in fluid communication with the reaction cavity for supplyingone or more reactants thereto, and—for continuous reactor operations—anoutlet port in fluid communication with the reaction cavity fordischarging a reactor effluent (including one or more reaction productsand one or more unreacted reactants) therefrom. Hence, in general, many,if not all, of the single microreactor designs reported in theliterature can be employed in connection with the present invention,including, for example, microchannel-type microreactors, cell-typemicroreactors, combined microflow (e.g., “Y”-shaped or “T”-shaped)reactors, electrochemical reactors, photochemical reactors, etc. Themicroreactors can have integrated microscale heat-control components,active microcomponents such as mixers, valves, etc., and/or passivemicrocomponents such as passive mixers. Such components can be dedicatedto service individual microreactors, or can be generic to several or toall of the microreactors of the chemical processing microsystem. Themicoreactors can be designed to model (or be indicative orrepresentative of) conventional, commercial-scale reactors such ascontinuous-stirred-tank reactors (CSTR's) and plug-flow reactors(PFR's), among others. With respect to heterogeneous catalyst screeningapplications, microreactors modeling CSTR's may, as discussed below, beadvantageously applied for primary screening tasks, and PFR's may bebetter suited for secondary screening tasks.

The number of microreactors included within the chemical processingmicrosystem is at least 2, preferably at least 4, more preferably atleast 7, still more preferably at least 10, more preferably still atleast 15 and even more preferably at least 20 for moderate throughputembodiments. In higher throughput embodiments, the number ofmicroreactors in the chemical processing microsystems is at least 25,more preferably at least 30, even more preferably at least 50, stillmore preferably at least 75, yet more preferably at least 100, and mostpreferably at least 250. Present microscale and nanoscale fabricationtechniques can be used, however, to prepare microsystems having an evengreater number of microreactors. For even higher throughput operations,for example, the number of microreactors can be at least about 400,preferably at least about 1000, more preferably at least about 10,000,even more preferably at least about 100,000, and most preferably atleast about 1,000,000 or more.

The number of microreactors may, however, be the same as or differentfrom the number of candidate materials being investigated, since some ofthe microreactors may be supplied with the same candidate material, leftas blank controls, or with supplied with positive or negative controlmaterials having known properties. For applications directed toidentifying new materials having a useful property of interest, at leasttwo or more, preferably at least four or more, in many cases most, andallowably each of the plurality of microreactors comprise at least aportion of one or more different candidate materials within the reactioncavity thereof. Specifically, a different candidate material can beincluded within at least about 50%, preferably at least 75%, preferablyat least 80%, even more preferably at least 90%, still more preferablyat least 95%, yet more preferably at least 98% and most preferably atleast 99% of the plurality of microreactors. For example, “X” differentcandidate materials being investigated can be individually resident inseparate, dedicated microreactors included in a microsystem having “Y”total microreactors as follows: 4 of 7, 8 of 15, 15 of 30, 25 of 50, 75of 100, 90 of 100, 225 of 250, and 950 of 1000. For some applications,however, it may be desirable to include different candidate materials ina smaller percentage of the total number of microreactors. For example,four or more different candidate materials can be evaluated as separate,parallel groups of materials, with each group of materials beingsubjected to different process conditions. More specifically forexample, four or more different candidate materials (e.g. A, B, C, D)can be evaluated in eighty microreactors as twenty groups of the fourdifferent materials with each of the twenty groups being subjected tovarious process conditions. In such a case, different candidatematerials occupy only 5% of the total number of microreactors. In thegeneral case, a different candidate material can be included within notless than about 5%, preferably not less than about 10%, more preferablynot more than about 20%, even more preferably not more than about 30%,and still more preferably not more than about 40% of the plurality ofmicroreactors. Particular examples, in which “X” different candidatematerials are investigated in. groups in a microsystem of “Y” totalmicroreactors, are as follows: 4 of 8, 4 of 12, 4 of 16, 4 of 40, 10 of20, 10 of 40, 10 of 50, 10 of 100, and 10 of 200. Other combinations,including both general schemes and specific arrangements are alsopossible and within the experimental design selection of a person ofskill in the art.

In preferred embodiments, the microreactors are arranged as an array ofmicroreactors that spatially corresponds to the array of candidatematerials. The microreactors are preferably arranged in a substantiallyplanar array (e.g., as shown in FIG. 2), but could also be arranged innon-planar array (e.g., as shown in FIG. 5). Hence, in preferredembodiments, the separation between adjacent microreactors (center ofreaction cavity to center of reaction cavity) can range from about toabout 50 μm to about 1 cm, more preferably from about 100 μm to about 7mm, and most preferably from about 1 mm to about 5 mm. Theinter-microreactor spacings can be not more than about 1 cm, not morethan about 7 mm, not more than about 5 mm, not more than about 4 mm, notmore than about 2 mm, not more 1 mm, not more than about 100 μm, and notmore than about 50 μm. Exemplary inter-microreactor spacings(center-to-center) based on preferred embodiments of the invention are 4mm for having 256 addressable regions on a three-inch wafer substrate,and 2 mm for having 1024 addressable regions on a three-inch wafersubstrate. As such, the planar surface density of microreactors canrange from about 1 microreactor/cm² to about 200 microreactors/cm², morepreferably from about 5 microreactors/cm² to about 100microreactors/cm², and most preferably from about 10 microreactors/cm²to about 50 microreactors/cm². The planar density can be at least 1microreactor/cm², at least 5 microreactors/cm², at least 10microreactors/cm², at least 25 microreactors/cm², at 50microreactors/cm², at least 100 microreactors/cm², and at least 200microreactors/cm². For moderate throughput systems, lower or mid-rangedensities may be preferred. For other, higher throughput systems, highermicroreactor densities are generally preferred. Additionally, evenhigher densities may be achieved as fabrication technology develops tonano-scale applications.

Regardless of the specific microreactor geometry or arrangement, each ofthe plurality of microreactors can be designed to be permanentlyintegrated with the array of candidate materials (e.g., by anodicallybonding the candidate-material-containing wafer to the microreactor-wellcontaining wafer), or can be releasably and preferably sealablyintegrated with the array of candidate materials being investigated(e.g., as described above), to facilitate efficient interchanging (thatis, loading, unloading and reloading) of candidate material libraries(e.g., arrays) with a reusable chemical processing Microsystems.

The microreactors included in the chemical processing microsystem arepreferably formed in a plurality of laminae. The laminae in which themicroreactors are formed can be integrated with, and in some embodimentsare preferably releasably integrated with, at least onematerial-containing laminate comprising the candidate materials beinginvestigated. In a preferred embodiment shown schematically in FIG. 8, amicroreactor 600 is formed in a plurality of laminae comprising a(material-containing) first laminate 100, and a composite reactor block200 comprising a (reactor) second laminate 220 adjacent to thematerial-containing first laminate 100 and a (capping) third laminate230 adjacent the reactor second laminate 220. A releasable seal 300 ispreferably situated between the material-containing first laminate 100and the reactor second laminate 220. The releasable seal can preferablywithstand the reaction conditions for the chemical reaction of interest.In general, the releasable seal can preferably withstand temperaturesgreater than 100° C., and preferably greater than about 200° C. Thereleasable seal can preferably withstand pressures greater than about 20bar; preferably greater than about 50 bar, and more preferably greaterthan about 100 bar. As an alternative to the releasable seal 300,however, the material-containing first laminate 100 and reactor secondlaminate 200 could be bonded to each other (e.g., anodically, or forsome applications, with an inert epoxy or other suitable adhesive).Preferably, such a bond can withstand the required reaction conditionsfor the chemical reaction of interest. In the general case, the bond canpreferably withstand temperatures of not less than about 100° C.,preferably of not less than about 200° C. and/or a pressure of not lessthan about 100 bar, preferably of not less than about 200 bar.

More specifically, with reference to FIG. 8, the material-containingfirst laminate 100 has a first surface 101, a second surface 102 inspaced, substantially parallel relationship to the first surface 101,and a circumferential edge 103. The reactor second laminate 220 has afirst surface 221 in releasable contact with the second surface 102 ofthe first laminate 100, a second surface 222 in spaced, substantiallyparallel relationship to the first surface 221, and a circumferentialedge 223. The capping third laminate 230 has a first surface 231 bondedto the second surface 222 of the reactor second laminate 220, a secondsurface 232 in spaced, substantially parallel relationship to the firstsurface 231, and a circumferential edge 233. The reactor laminate andcapping laminate can be of any material suitable for the reactionconditions. The capping laminate may, for example, be photo-transmittingfor use in connection with photochemical reactions. The reactor secondlaminate 220 further comprises interior edges 224 and an interiorsurface 225 defining an aperture (with corresponding void space) in thesecond laminate 220, such that, taken together, the second and thirdlaminates 220, 230 form a composite substructure, reactor block 200,comprising a well defined by the interior edge 224 and interior surface225 of the second laminate 220 and those portions of the first surface231 of the third laminate circumscribed by such interior edge 224. Asnoted, the material-containing laminate 100 can be bonded or releasablyengaged with at least one of the adjacent laminates, and preferably,with at least the reactor block 200. A bonded contact between thesesurfaces may be preferred for higher pressure applications and/or forsingle-loading systems (e.g., disposable systems, or for catalyst thatdo not readily foul or which can be regenerated in situ). Formultiple-loading systems, the releasable contact between the reactorsecond laminate 220 and the material-containing first laminate 100 canbe provided by a releasable seal 300 such as a solid gasket, gasketdressing, and/or other suitable material. The material-containinglaminate 100 is also preferably in releasable contact with (andreleasably engaged with) a surface of any other adjacent laminate, suchas the temperature-control block 400. Each of the laminae materialsshould be compatible with the chemical process of interest, includingwith respect to resistance to chemical degradation, temperature andpressure considerations, heat transfer considerations, fabrication(including bonding and/or sealability), etc.

The material-containing laminate 100 further comprises a candidatematerial 120 (a) known to have catalytic activity for a gaseous chemicalreaction, (b) being screened for catalytic activity for a gaseouschemical reaction, or (c) operating as a control material therefor(including the substrate material serving as a blank control). Thecandidate material 120 can be on formed on an exposed surface of thefirst laminate 100—as shown in FIG. 8, on a surface 112 of a well 130formed in the material-containing first laminate 100. The well in thematerial-containing laminate is defined by material-containing surface112, interior edges 114 and interior surface 115. Taken together, thefirst, second and third laminates 100, 220, 230 form a microreactordefined by the interior edges 224 and interior surface 225 of the secondlaminate, by the interior edges 114, interior surface 115,material-containing surface 112 and the candidate material 120 of thefirst laminate 100, and by those portions of the third laminate 230circumscribed by the interior edges 224 of the second laminate.

With respect to fluid distribution, the microreactor 600 furthercomprises a reactor inlet 250 formed as a microfluidic channel 251between the second and third laminates 220, 230, and a reactor outlet260 formed as an interior surface 261 defining an aperture in the thirdlaminate 230. The inlet 250 is preferably in fluid communication with amicrofluidic distribution system, such as that described in connectionwith FIG. 7B (with the microfluidic channel 251 of FIG. 8 correspondingto a terminal channel section 517 of FIG. 7B). The outlet 260 ispreferably in fluid communication with analytical devices and/orinstrumentation, as discussed in further detail below.

The microreactor, such as that shown in FIG. 8, may further comprise oneor more ports (not shown in FIG. 8) for analytical microinstruments(e.g., temperature and/or pressure monitoring) and/or for processcontrol elements (e.g., pressure-relief valves). The microreactor mayalso comprise a temperature-control block 400. The temperature-controlblock 400 can be a heating block (useful, for example for maintainingreaction temperature in a reactor during an endothermic reaction), acooling block (useful, for example, for maintaining reaction temperaturein a reactor during an exothermic reaction), or an insulator block(useful, for example, for providing adiabatic or quasi-adiabaticconditions during a reaction). As discussed below, the temperature ofthe temperature-control block can be controlled to maintain the sametemperature for the plurality of microreactors, or alternatively, toprovide a different temperature for a plurality of microreactors, or toprovide a different temperature for each of the microreactors. As shownin FIG. 18E and discussed in connection therewith, fine tuning of thetemperature profile can be achieved using additional heating elementsintegral with the material-containing laminate or integral with amicroreactor support laminate (block) adapted to receive thematerial-containing laminate.

A plurality of microreactors, such as the preferred embodiment shown inFIG. 8, can be fabricated in a plurality of laminae using microscale andnanoscale fabrication techniques known in the art. With reference now toFIGS. 9A and 10A through FIGS. 9I through 10I, respectively, forexample, a plurality of composite reactor blocks 200 having an integralfluid distribution system, such as the supply distribution system 500shown on FIG. 7B, can be fabricated in a reactor first laminate 220 anda capping second laminate 230. The fluid distribution system, as shownin FIGS. 9A and 10A, includes a supply distribution channel 514 in fluidcommunication with a reactor inlet port (the location of which isgenerally indicated at 250), and a discharge distribution channel 261 influid communication with reactor outlet port 260.

Briefly, to fabricate a plurality of reactor blocks 200, an etch-mask270 (e.g., low-stress silicon nitride, Si₃N₄, 500 nm) is deposited bychemical vapor deposition onto an exposed first surface 231 of thecapping second laminate 230 (FIG. 9B-9C, FIG. 10B-10C) (e.g., 100 mmsilicon, <100>). A photoresist layer 272 (e.g., Shipley 1813) isphotolithographically patterned and developed (e.g., with MF-319) ontoan exposed surface of the etch mask 270 (FIG. 9D, FIG. 10D). Thepatterned photoresist layer exposes a plurality of desired portions 273,274 of the surface of the etch mask 270. Exposed portions 273 can be,for example, a circular shape, and exposed portions 274 can be designedto correspond to the desired supply distribution manifold. The etch mask270 is then selectively etched (e.g., SF₆CF₃Br plasma etch) and theremaining photoresist layer 272 is subsequently stripped (e.g., sulfuricacid/hydrogen pyroxide, 4:1) (FIG. 9E, 10E), to expose desired portions233, 234 of the first surface 231 of the first laminate 230. The exposedportions 233, 234 of the laminate 230 are then selectively etched (e.g.,with KOH (22.5%, 80° C.)) to form shallow wells 235′ and the supplydistribution channel 514 in the first laminate 230. (FIG. 9F, FIG. 10F).An aperture defining discharge distribution channels 261 and the reactoroutlet ports 260 can be provided through the first laminate 230 (e.g.,by drilling with a YAG laser). (FIG. 9G, FIG. 10G). The aperture canextend from the well 235′ surface to the second surface 232 of thesecond laminate 230. The etch mask 270 can then be stripped from thesecond laminate 230, (FIG. 9H, FIG. 10H) to form a subassembly of thesecond laminate 230 (having a shallow well 235′ and a fluid distributionsystem (514, 250, 260, 261) integral therewith). Referring now to FIGS.9I and 10I, a plurality of apertures defining interior edges 224 andinterior surface 225 can be formed in the reactor first laminate 220(e.g., by ultrasonically drilling the, e.g., glass laminate), with theaperture extending from a first surface 221 to a second surface 222 ofthe laminate 220, to form a subassembly of the first laminate 220(having a plurality of apertures). The first and second laminate 220,230 subassemblies can then be bonded (e.g., anodically bonded) to formthe reactor block 200 of FIGS. 9A and 10A having a plurality of reactorwells 235.

With reference to FIG. 8, the plurality of microreactors can then beassembled by releasably combining the composite reactor block 200 and amaterial-containing array 100 with a releasable seal (e.g., gasket)therebetween. The seal can be prepared from any suitable material. Theseal materials can be thin metal foils, such as Cu, Au, Ag, Al, Ni, orcombinations thereof (e.g., Au-coated Cu). Quart (e.g., quartz paper,impregnated quartz paper), and graphite foil can also be suitable gasketmaterials for many applications. Polymeric materials such as TEFLON(e.g., expanded polytetrafluoroethlene (PTFE)), polyimides, variouselastomers, etc., combinations thereof, or combinations thereof withother materials (e.g. metals, graphite) may be suitable for other,relatively lower temperature applications. The gasket seal can beprepared from sheets of such materials (e.g., “quartz paper”) byproviding apertures (e.g., by punching or drilling) arranged tocorrespond to the reactor wells 235′ and/or portions of the array 100that include the candidate materials 120). A second releasable material(not shown) may be provided between the material-containing array 100and the heating block 400 or other support block adjacent the oppositefirst side 101 of the array 100.

Several microreactor design parameters are typically considered withrespect to designing a microreactor for a particular chemical process ofinterest. Such design parameters include, without limitation, themicroreactor volume, the microreactor geometry (e.g., shape), the inletport location and sizing, the outlet port location and sizing, and thetype, amount, surface area and/or the relative location of the candidatematerial being investigated, among others. In general, the microreactordesign parameters can be constrained by the desired process conditions(e.g., reaction conditions) required for the process being investigated,as discussed in greater detail below with respect to a preferred,diffusion-mixed microreactor design. Nonetheless, the microreactordesign parameters can vary substantially, from application toapplication, to suit particular needs, and still be within the scope ofthe invention. As such, the following exemplary design parameters are tobe considered as non-limiting, except as specifically recited in theclaims.

Microreactor volume is defined as the physical volume of the reactioncavity—that is the physical volume of the space in which the reaction(or other chemical process of interest) is allowed to occur. As such,the microreactor volume can be designed, in combination with avolumetric flow rate through the reaction cavity, to obtain a residencetime, τ_(res,) sufficient to effect the reaction (or other chemicalprocess) of interest. The microreactor volume can be, in general, lessthan about 10 ml, less than about 5 ml, less than about 3 ml, andpreferably, less than about 1 ml. For many applications, themicroreactor volume is even more preferably less than about 100 μl, yetmore preferably less than about 10 μl, and most preferably about 1 μl.The volume can range, for example, from about 1 nanoliter (nl) to about10 ml, preferably from about 1 nl to about 1 ml, more preferably fromabout 10 nl to about 100 μl, even more preferably from about 0.1 μl toabout 10 μl, and most preferably from about 0.5 μl to about 5 μl. Whilea volume of about 1 μl is suitable for many applications, other volumesmay be desired or necessary for certain applications and/or certainreactions.

The microreactor geometry can be of any suitable shape or geometry, butfor some designs—such as diffusion-mixed microreactors as describedbelow—is preferably a cell-type microreactor rather than a channel-typemicroreactor. For purposes herein, the distinction between a cell-typemicroreactor and a channel-type microreactor can be characterized withrespect to a ratio of three distances, X:Y:Z, measured within thereaction cavity along three mutually orthogonal lines having a commonpoint of intersection, where Z is considered, by definition herein, tobe the longest distance, where the common point of intersection is themidpoint of the line defining the Z distance, where Z is normal to atleast one surface which it intersects, and preferably to two surfaceswhich it intersects, and where the XYZ coordinates are positioned (e.g.,through rotational freedom) such that each of the three distances aremaximized, to the extent possible. The XYZ ratios for a variety ofcommon three-dimensional shapes are depicted schematically in FIGS. 11Athrough 11F. Characterized in this manner, the microreactor geometriesare preferably designed such that X:Z and Y:Z ratios each, independentlyrange from about 1:2 to about 1:1. The X:Z and Y:Z ratios each morepreferably range, independently, from about 2:3 to about 1:1 and evenmore preferably from about 3:4 to about 1:1. A most preferred X:Z andY:Z ratios are each, independently, about 0.9:1. Microreactors having ageometry characterized by such ranges of X:Z and Y:Z ratios can beadvantageously employed as diffusion-mixed microreactors, as discussedbelow.

The inlet and outlet port sizes can vary, depending primarily onreactant flow, on pressure, and for some designs such as diffusion-mixedmicroreactors, on back-diffusion considerations. Inlet and outlet portscan have dimensions (e.g., length of one side of a square and/ordiameter) that range from about 1 μm to about 2 mm, preferably fromabout 10 μm to about 1 mm, and more preferably from about 10 μm about100 μm. In terms of hydraulic radius, the inlet and/or outlet ports canhave a hydraulic radius ranging from about 0.125 μm to about 0.5 mm,from about 0.25 μm to about 250 μm, and preferably from about 2.5 μm toabout 100 μm. The location of the inlet and outlet ports isnon-limiting, except that, in preferred embodiments as noted above, theyare arranged so that the structural integrity thereof is independent ofthe material-containing array.

The specific surface area, amount, location and type of candidatematerials is also highly process dependent. For heterogeneous catalystscreening, for example, catalyst surface areas can range from about 0.1m²/g to about 2000 m²/g, and preferably from about 1 m²/g to about 100m²/g. The amount of catalyst material and location can be varied asdiscussed above. In preferred applications, in which a film of thecandidate material being investigated is formed on a surface which is orbecomes a reaction-cavity-defining surface, the candidate material canbe comprise from about 1% to about 100% of the reaction-cavity surface.In typical applications, however, the candidate material comprises fromabout 10% to about 70% of the reaction-cavity surface, and preferably insome cases, from about 20% to about 50% of the reaction-cavity surface.

Reaction Conditions

Regardless of the particular microreactor design, the plurality ofnicroreactors in a chemical processing microsystem are preferablydesigned such that the reaction process conditions can be controlled tobe substantially identical in each of the plurality of microreactors.Chemical processing Microsystems having substantially identical processconditions are particularly suitable for screening a library ofdifferent candidate materials—to allow for direct comparison between thedifferent candidate materials at those maintained reaction conditions.In a preferred embodiment, therefore, the plurality of microreactors aresubstantially identical for each of the microreactors included inchemical processing microsystem.

Alternatively, however, the reaction conditions can be controllablyvaried amongst the plurality of microreactors—either between one groupof microreactors and another group of microreactors, or between each ofthe plurality of microreactors. Varied reaction conditions can beemployed, for example, using an array of different candidate materialsin repetitive experiments to determine whether certain reactionconditions favor certain of the candidate materials, or to determine arange of conditions for which certain candidate materials have theproperty of interest. As discussed below, varying of reaction conditionscan also be employed using an array comprising a single material (e.g.,catalyst) for process research and optimization. Exemplary reactionconditions that can be readily varied include temperature, pressure andresidence times, among others.

Several process conditions are typically of importance in connectionwith chemical processes, and particularly, in connection with chemicalreactions. Such process conditions include primarily, withoutlimitation, temperature, pressure and reactant residence time (e.g.,reactant contact time with a catalyst). Selection of such parameterswill vary with the particular reaction of interest, and/or for theparticular research goals of interest. As such, a person of skill in theart can vary these parameters and others to suit their particular needs,and still be within the scope of the invention. Hence, the followingexemplary design parameters are to be considered as non-limiting, exceptas specifically recited in the claims.

Temperature in a reaction cavity and/or temperature of a candidatematerial of interest can be controlled by any suitabletemperature-control device (e.g., heat transfer apparatus) known in theart for microfluidic applications. While such a device can be integratedinto the chemical processing microsystem of the present invention in anysuitable manner, the structural integrity of such device is preferablyindependent of the material-containing array. With reference to FIG. 2and FIG. 8, for example, a temperature-control block 400 can operate asa heat sink (e.g., to maintain approximately constant temperature duringa exothermic reaction), as a heat source (e.g., to maintainapproximately constant temperature during an endothermic reaction), oras an insulator (e.g., to provide approximately adiabatic reactionconditions). The temperature-control block 400 can be, for example, amicrofluidic heat exchanger (See, for example, U.S. Pat. No. 5,811,062to Wegeng et al.), or a microscale resistive heating element. Thetemperature can be maintained substantially the same in each of themicroreactors, or can be varied between groups of microreactors orbetween each of the microreactors. For example, a temperature gradientcan be spatially applied across one or more directions of amaterial-containing array. As another example, spatially addressableindependent heating elements can be used to individually control thetemperature of each microreactor (or each candidate material). See, forexample, U.S. Pat. No. 5,356,756 to Cavicchi et al. Appropriatemicroscale temperature-sensing devices, together with a suitable processcontrol system, can also be employed. See, for example, S. M. Sze,Semiconductor Sensors, John Wiley & Sons, Inc. (1994).

Pressure in a reaction cavity can be controlled on a microscopic scaleby a number of different approaches. For example, the fluid pressure-inthe reaction cavity can be varied by actively controlling the flowresistance (e.g., with a microscale pressure-control valve) in thesupply manifold or in the discharge manifold. In a passive microfluidicdistribution system—lacking any active pressure-control components suchas valves—pressure considerations are typically factored into themicroreactor and distribution system design, by variation of flowconductance of either the supply or discharge manifold. For a systemhaving an established microreactor design and an established passivedistribution design, the pressure in the microreactor can be controlledby varying the supply pressure, varying the discharge backpressureand/or varying the reactant flow rates through the distribution system.Pressures can be maintained substantially the same in each of themicroreactors, or can be varied for a group of microreactors or for eachindividual microreactors (for example, by varying the conductance of thedistribution channel serving a group of microreactors or eachmicroreactor. Appropriate microscale pressure-sensing devices, togetherwith a suitable process control system, can also be employed. See Sze,Id. In general, for the preferred embodiments of the invention, higherpressures can be achieved by using microreactors formed in bonded,rather than releasably-sealed laminae—especially when the microsystemitself is under atmospheric conditions. Microreactors formed inreleasably-sealed laminae can also be employed at higher pressures byplacing the entire microsystem into a hyperbaric chamber such that thepressure difference between the reaction cavity and the atmosphereexternal to the microsystem is within the sealing capabilities of thereleasable seal.

Residence time in a reaction cavity can be designed based onmicroreactor volume and reactant flow rate through the microreactor.Flow rates are, in turn, dependent upon reactor inlet port and outletport geometries, distribution system geometries and fluid pressures.Residence times can be maintained substantially the same for each of themicroreactors or can be varied for a group of microreactors or for eachof the microreactors. In one embodiment, a plurality of microreactorssuitable for providing varying residence times for differentmicroreactors is provided by fabricating the microreactors with varyingvolumes. With reference to FIG. 9, for example, the volume of eachreactor well 235 could be varied between one group of microreactors andanother group, or between each individual microreactor. In analternative embodiment, a flow-distribution system suitable forproviding varying residence times for different microreactors (nowhaving substantially the same volume) is provided by fabricating flowdistribution networks having varying flow restriction (andcorrespondingly varying conductance) between different flow channelssuch that the flowrates to different microreactors (or sets ofmicroreactors) varies. With reference to FIG. 7B, for example, the totalflow restriction of each flowpath could be varied between flowpaths toone group of microreactors and another group, or between flowpaths toeach individual microreactor. In any case, appropriate microscaleflow-sensing devices, together with a suitable process control system,can also be employed. See Sze, Id.

Applicable actual temperatures, pressures and residence times will varysignificantly for different processes of interest. Generally, for manychemical reactions of interest, temperatures are preferably above about100° C., and more preferably above about 200° C. Pressure can generallyrange from about atmospheric pressure to 200 bar. Exemplary reactionconditions for heterogeneous catalysis applications are as follows. Thetemperatures for heterogeneous catalysis can typically range from about0° C. to about 1200° C., preferably from about 25° C. to about 800° C.,more preferably from about 100° C. to about 800° C., and most preferablyfrom about 100° C. to about 500° C. Pressures for heterogeneouscatalysis can typically range from about atmospheric pressure to about200 bar, from about atmospheric pressure to about 100 bar, and fromabout atmospheric pressure to about 50 bar. Vacuum conditions arecontemplated for some chemical reactions or other chemical processes(e.g., separations). Residence times for heterogeneous catalysis canrange from about 1 μsec to about 1 hr, preferably from about 100 μsec toabout 30 minutes, more preferably from about 1 msec to about 15 minutes,and most preferably from about 10 msec to about 2 minutes. FIG. 12 showsthe reaction temperature and residence times required for variousheterogeneously-catalyzed reactions of commercial significance usingknown commercial catalysts.

Diffusion Mixed Microreactors—Microreactor Design and ReactionConditions

In a preferred embodiment, materials that enhance a chemical reaction ofinterest, such as heterogeneous catalysts, can be identified in aplurality of continuous flow microreactors—where each of themicroreactors are designed and the process conditions are controlledsuch that the residence time, τ_(res,) of reactants in the reactioncavity is sufficient to provide for diffusion mixing thereof, andpreferably, without substantial back-diffusion of the reactants throughthe reactant inlet port.

Diffusion mixing occurs when two or more different fluid molecules arecompletely mixed by diffusion, without the assistance of active mixingelements (e.g., impellers, motors) and without the assistance of staticmixing elements (e.g., turbulence generated by flow through atortuous-channel). While some localized mixing may occur due to flow(e.g., near a microreactor inlet port), the mixing in the reactioncavity of diffusion-mixed microreactors is ascribable predominantly todiffusion phenomena. In general, diffusion mixing will occur when themicroreactor is designed and the process conditions are controlled suchthat that the residence time, τ_(res,) of reactants in the reactioncavity is greater than the diffusion period, τ_(diff,) for the reactantsin the reaction cavity. Qualitatively, this suggests that diffusionmixing can occur with relatively long residence times and relativelyshort diffusion periods—conditions generally achievable with very lowflow rates through small, cell-type microreactors (having smalldiffusion paths).

A diffusion-mixed microreactor can be designed by controlling reactorgeometry and reaction process conditions. The diffusion period,τ_(diff,) can be defined as the time required for a reactant molecule todiffuse through a mean free path that is equal to the longest path ofdiffusion, L_(diff,) for a particular microreactor design. The longestpath of diffusion, L_(diff,) can be defined as equal to the longeststraight-line dimension for a reaction cavity of a particular geometry.For a relatively flat, circular reaction cavity such as shown in FIG.11E (and substantially as that shown in FIGS. 9A and 10A), for example,the longest path of diffusion, L_(diff,) is the diameter, d. For along-channel type microreactor, such as is represented by FIG. 11D, thelongest path of diffusion, L_(diff,) is the length, l. Hence thediffusion period, τ_(diff,) will be a function of the reactantdiffusivity, D, and the longest path of diffusion, L_(diff,) and can becalculated, based on a one-dimensional model, as set forth in Equation3a:τ_(diff,)=(L _(diff))² /D   Eqn. 3a.While a one-dimensional model can be satisfactory as a conservativeapproximation for many reactor geometries, L_(diff,) can likewise becalculated, based on a two-dimensional model. Diffusivity, D, is, inturn, dependent upon the particular reactant fluid and the temperature,T, of the reactant fluid within the reaction cavity. As such, bothmicroreactor design parameters and process conditions can affect thediffusion period, τ_(diff). The residence time, τ_(res,) is a functionof reaction cavity volume, V, and reactant flowrate, V, and as such, islikewise dependent upon both microreactor design parameters and processconditions. The residence time can be calculated as shown in Equation 4:τ_(res) =V/V   Eqn.4Hence a diffusion-mixed microreactor can be designed by varying reactorgeometry (e.g., longest path of diffusion, L_(diff,) and/or reactioncavity volume, V) and/or by varying reaction process conditions (e.g.,temperature, T, flowrate, V).

In a preferred approach, a diffusion-mixed microreactor can be designedfor combinatorial chemistry research purposes directed towardidentifying materials as follows. Once the chemical reaction of interestis identified, a target temperature, T, and a target residence time,τ_(res,) can be chosen. These variables can be chosen, for example,based on industry standards, or based on research goals that improve onindustry standards by a certain margin. With reference to FIG. 12, forexample, temperature and residence time for the heterogeneous catalysisreaction of automobile catalytic converters can be chosen as a targettemperature of about 600° C. and a target residence time of about 0.1seconds (current industry standard) or, alternatively, as a targettemperature of about 600° C. and a target residence time of about 0.01seconds (reduced by factor of ten relative to current industrystandard). The diffusivity, D, of the reactants can then be calculatedat that known target temperature, T. The longest path of diffusion,L_(diff,) is then determined by applying the definitional requirementfor diffusion-mixing: that the residence time be greater than thediffusion period (τ_(res)>τ_(diff)). Substituting from Equations 3a(based on one-dimensional model, for example) and 4, and rearrangingyields Equation 5, from which L_(diff,) can be calculated:L _(diff)=[(D)(τ_(res))]^(1/2)   Eqn. 5.Knowing L_(diff,) a reactor geometry can be selected and a reactioncavity volume, V, can then be calculated to provide that L_(diff) basedon that geometry. Now knowing V, the required volumetric flowrate, V,can be calculated using Equation 4. The reactor inlet port and reactoroutlet port dimensions and distribution manifold particulars can then bedesigned to provide the required flowrate.

In preferred embodiments, diffusion-mixing occurs without substantialback-diffusion of reactants into the reactant supply manifold.Back-diffusion of the reactant molecules through the reactor inlet portis substantially avoided by ensuring that the flow velocity at thereactor inlet port, v_(flow,) is greater than the diffusion velocity,v_(diff). Based on this principle, a reactor inlet dimension (assumingcircular cross-section) can be determined from Equation 6:r<[Q(L _(diff))/(D)(π)(P)]^(1/2)   Eqn. 6,where r is the radius of a circular reactor inlet port, Q is thepressure-velocity per unit time and P is the pressure in themicroreactor. As explained above, inlet pressure, P, is dependent, inturn, on flow-rate, V, and on the distribution system conductance.

Diffusion-mixed microreactors can model a continuous-stirred-tankreactor (CSTR)—but without any active mixing elements (e.g., impellers,motors) and without any static mixing elements (e.g., atortuous-channel). As such, a diffusion-mixed microreactor offerssubstantial advantages over microreactors/reaction conditions designedto model a plug-flow reactor (PFR) in applications directed toidentifying new catalysts or other new materials. With reference toFIGS. 13A through 13C, an ideal plug-flow reactor has a residence timedistribution function approaching a delta function (FIG. 13A)—that is,each molecule of a reactant sample will have the designed residencetime. A non-ideal, (e.g., commercial) plug-flow reactor has a relativelynarrow residence time distribution function (FIG. 13B)—such that most ofthe molecules in the sample will, with high probability, have thedesigned residence time, but some relatively small number of moleculeswill reside in the reaction cavity for a time that is less than or morethan the designed residence time, but in a narrow time interval withrespect to the designed residence time. In contrast, however, acontinuous-stirred-tank reactor has a relatively broad residence timedistribution function exhibiting an exponential decay (FIG. 13C)—suchthat, while some of the molecules in the sample will have someprobability of residing in the reactor for the designed residence time,many of the molecules in the sample will reside in the reaction cavityfor a time that is less than or more than the designed residence time,and in a relatively broad time interval with respect to the designedresidence time. The broader range of residence times can be advantageousfor combinatorial materials science research, and especially for primaryscreening approaches, because of the larger process-condition space thatis effectively investigated in parallel with a single microreactordesign, which could lead to a greater number of primary screen hits in asingle screening experiment.

The diffusion-mixed microreactors of the present invention can beapplied as single microreactors—for example, for microscalemanufacturing, or alternatively, a plurality of such microreactors canbe used in a chemical processing microsystem for characterizing oroptimizing chemical reaction processes and/or for identifying andoptimizing materials (e.g., catalysts) that enhance a chemical process.

Discharging Reactor Effluents from the Microreactors

As noted, the plurality of microreactors are preferably designed tooperate as continuous reactors, rather than as batch reactors. As such,the reaction products, if any, and the excess reactants, if any, aredischarged, preferably simultaneously discharged, from each of themicroreactors. With reference again to FIG. 1A, the reactor effluentstream can be discharged to waste and/or, as discussed below, wholly orat least partially discharged to analytical devices and instrumentationfor evaluation of the candidate materials.

The particular design details of a reactor effluent manifold are not, inthe general case, of substantial critical significance. In general, thereactor effluent streams can be discharged from the plurality of reactoroutlet ports (e.g., outlet port 260 in FIG. 8) as a plurality ofindependent streams (e.g., as waste streams and/or as analytical samplestreams)—without recombining the streams. The reactor effluent streamscan, alternatively, be recombined, partially or completely, afterdischarge from the plurality of microreactors. In any case, many of thedesign considerations discussed above in connection with the supply ofreactants to the plurality of microreactors are also applicable withrespect to discharge of the reactor effluent. For example, pressurecontrol can, additionally or alternatively to other pressure-controlapproaches, be realized through an effluent distribution manifold byproviding flow resistance in the effluent flow path. If desired tomaintain substantially the same reaction conditions for eachmicroreactor, however, the effluent manifold paths are preferablydesigned to be symmetrical (i.e., with equal conductance).

FIG. 14 shows a preferred binary-tree effluent manifold 501 for use inconnection with the present invention, in which each of a plurality ofmicroreactors 600 are in fluid communication with a common effluent port510, and the flow paths from each of the microreactors 600 to commonport 510 have equal conductance. The effluent distribution manifold 501can comprise, more specifically, 2^(n) terminal ports 520 adaptable forreceiving fluid the 2^(n) microreactors 600 (or, in the general case,other microcomponents), and a distribution channel (generally indicatedas 514) providing fluid communication between each of the 2^(n) terminalports 520 and the common port 510 (via common header 512). The remainingdetails of the effluent distribution are, except as noted below,substantially the same as those described in connection with the supplyof reactants to the microreactor. As noted above in connection with thesupply manifold, the effluent distribution manifold can have a singlecommon port 510 located centrally or near the peripheral edge of themanifold.

In a preferred embodiment, the effluent manifold serves as fluidcollection function, but is not used for pressure control. As such, thechannel dimensions for each of the distribution channels 514 areapproximately the same over the entire flow length of the channel, andthe conductance, C, (for rectangular cross-sections having a width, wand height, h, being proportional to wh³ and for aspect ratios of about1, proportional to approximately h⁴) for the effluent manifold is about100 times greater than the conductance, C, of the supply manifold. In apreferred embodiment, therefore, the dimensions of the effluent manifoldare approximately 100 μm for both height and width.

FIGS. 7G and 7H show alternative embodiments for reactor effluentdistribution systems. Briefly, effluent distribution channels 513 (FIG.7G, FIG. 7H) provide a discharge path for the plurality of microreactors600. As shown in FIGS. 7G and 7H, the highest pressure drop occurs inthe supply distribution channels 514 (“L-shaped”—FIG. 7G, or“binary-tree”—FIG. 7H) rather than in the effluent distribution channels513. To ensure substantially the same pressure and flow conditionsthrough each of the microreactors 600, the various flow-paths of each ofthe channels 513 are of the same length and equivalent geometry.

Evaluation of Candidate Materials

The plurality of candidate materials are screened to evaluate theircapability to enhance the chemical process of interest. In general, thecandidate materials can be screened during the chemical process—eitherby in situ measurements in the reaction cavity, or by measurements ofthe reactor effluent stream. The measurements can provide for real-timedirect evaluation of the candidate materials, or may, alternatively,provide for an indirect evaluation approach including a real-timestorage record of physical evidence or data that can be evaluated at alater time and/or at a remote location. For example, the evaluation ofcandidate materials can include a real-time separation of one or morecomponents that are indicative of the candidate material performance,with a subsequent quantitative determination thereof. In any case, theanalytical system for screening the candidate materials can be whollyintegral with the chemical processing microsystem, partially integraltherewith, or completely independent therefrom. Integral microcomponentscan include, for example, microscale probes and/or microsensorsincorporated into the microreactor design, microelectronic controlmodules integrated into the chemical processing microsystem, and/ormicroseparators integral with the chemical processing microsystem, asdiscussed in connection with FIG. 1C. Such systems can be whollyintegral, or combined with external instrumentation (e.g., detectors).

The particular approach employed for screening the candidate materialscan vary substantially, depending on the type of chemical process andthe enhancing property being evaluated. For chemical reactions, forexample, analytical measurements can determine the extent of thereaction (e.g., by considering product yield or reactant consumption),the rate of the reaction (i.e., kinetics), the extent or rate of anyside reactions, and properties as catalytic activity (i.e., turnover),selectivity in converting reactants into desired products, and stabilityduring operation under a wide variety of substrate concentrations andreaction conditions. Spatially selective characterization methodsinclude, for example, those capable of: (i) identification andcharacterization of gas phase products and volatile components of thecondensed phase products; (ii) identification and characterization ofcondensed phase products; and (iii) measurement of physical propertiesof the catalyst elements. Similar high throughput methodologies can beused for measuring properties of other than catalytic reactions.

Many different approaches and equipment configurations can be employedto effect screenings of the array of candidate materials. In oneembodiment, for example, each microreactor effluent stream can bedetected by discharging each reactor effluent stream directly to adetector—in rapid-serial fashion (e.g., using a single detector), inserial-parallel fashion (e.g. serially employing a group of paralleldetectors, where the group number is less than the number of candidatematerials to be evaluated), or in wholly parallel fashion (e.g., usingparallel detectors to screen each of the microreactions at the sametime). The detectors for gaseous reaction effluents can include, forexample, mass-spectrometers (e.g., capillary mass-spectrometers) or gaschromatographs (e.g., especially rapid gas chromatography approaches,such as those employing capillary bundles). In another embodiment,reaction products or quantitatively representative samples thereof maybe selectively separated and collected from the reactor effluent streamby chromatographic techniques (e.g. thin-layer chromatography plates;adsorption onto adsorbent media), and then subsequently evaluated. Asyet another approach for separating and collecting gaseous reactantproducts for evaluation, such products can be condensed (collectively,or in some applications, selectively) on a cold substrate, and thensubsequently evaluated.

Regardless of the approach or the equipment employed (i.e., whether massspectroscopy or gas chromatograph, etc., and whether parallel or serial,etc.), the evaluating of a particular candidate material preferably hasan overall throughput of at least about 1 candidate material/fiveminutes, more preferably at least about 1 candidate material/2 minutes,and most preferably at least 1 candidate material/minute, or faster.Substantially higher screening throughputs can be achieved usingparallel analytical measurement approaches. As such, the overall timerequired to identify materials having a reaction-enhancing property,more specifically defined as a difference in time, t₁−t₂, measured asthe time required to load the at least four candidate materials into thefour or more microreactors (such loading commencing at a time t₁), tosupply one or more reactants to the four or more material-containingmicroreactors, to contact the at least four candidate materials with theone or more reactants under conditions whereby the chemical reaction, ifany, is effected, to discharge the reactor effluents, and to evaluatethe at least four candidate materials for catalytic activity (suchevaluating being completed at a time t₂), being less than about 3 hours.The difference in time, t₁−t₂, is preferably not more than about 1 hr,more preferably not more than about 30 minutes, and even more preferablynot more than about 15 minutes. Hence, the overall candidate-materialthroughput (e.g. for catalytic activity) can be, depending on how manycandidate materials are evaluated in parallel, not less than about 1candidate material/hour, not less than about 10 candidatematerials/hour, more preferably not less than about 100 candidatematerials/hour, even more preferably not less than about 1000 candidatematerials/hour, and most preferably not less than about 1 candidatematerial/second.

With reference to FIG. 1C, a preferred screening approach forcharacterizing chemical reactions is based on separation of one or morereaction products (or, less preferably, of unreacted reactants) fromeach microreactor effluent stream, preferably by means of amicroseparator 900 that is integral with the chemical processingmicrosystem 10, followed by detection of the separated component,preferably by a detection system 1000. While the detection system 1000could also be integrated with the chemical processing microsystem 10, itis preferably configured external thereto and independent therefrom, toprovide for maximum flexibility with respect to available detectionapproaches.

In a preferred embodiment, the separation of one or more reactoreffluent components is accomplished based on adsorption principles. Sucha component (e.g., reaction products) can be selectively adsorbed ontoan adsorbent media, and subsequently determined. The reactant productsfor each of the microreactors are preferably adsorbed simultaneously, inparallel, onto the adsorbent material. The adsorbent material and theprocess of adsorption can be integral with or separate from the chemicalprocessing microsystem. Likewise, the analytical equipment and theprocess of determining reaction products can likewise be integral withor separate from the chemical processing microsystem. In a preferredapproach, however, a plurality of adsorbent materials and the process ofadsorption are integrated with the plurality of microreactors, but thedetermination of reaction products and the analytical equipment employedin such determination are independent of the chemical processingmicrosystem. The details of a preferred embodiment are presented below.Such an approach offers substantial flexibility with respect to theevaluation of candidate materials, and improves overall screeningthroughput.

The adsorbent media can be any adsorbent material that is selective forone or more particular reaction products, and/or particular unreactedreactants of interest. A wide variety of adsorbents are known in theart, for example, for use with thin-film chromatography, thermaldesorption and other chemical separations. Exemplary adsorbent materialsinclude silica gel (e.g., for selective adsorption of aniline and/orphenol over benzene), activated charcoals, graphitized carbon blacks,carbon molecular sieves and porous or non-porous polymers. (See,generally for example, SUPELCO catalog re “adsorbents”). The degree ofselectivity of the adsorbent material over the background materialsshould be sufficient to be of value with respect to the type ofscreening at issue. For example, while a fairly quantitatively sensitiveselectivity may be desired for a secondary screen, a relative lessquantitative screen may be suitable for primary screen. The adsorbentmaterial can be a composition that includes, in addition to a selectiveseparation media, one or more indicators (e.g. dyes) for an analyte ofinterest.

The plurality of adsorbent materials are preferably supplied to thechemical processing microsystem as an array of adsorbent materials. Anarray of adsorbent materials generally comprises a substrate and one (ormore) different adsorbent materials at separate portions of thesubstrate. The adsorbent materials may be located at discrete,individually addressable regions of the substrate or, alternatively, maybe contiguous with each other. The substrate material is selected to besuitable for support of the adsorbent, and is also preferably selectedfor suitability in connection with microfabrication techniques. Silicon,including polycrystalline silicon or single-crystal silicon, and silica(SiO₂) are preferred substrate materials. The substrate is preferably,but not necessarily, a substantially planar substrate, and the adsorbentmaterials are preferably, but not necessarily, arranged on the substratein a substantially co-planar relationship with each other.

The adsorbent media can have a number of different configurationsrelative to the plurality of microreactors. For example, eachmicroreactor effluent stream can be passed over, around or throughindependent adsorbent media supported by independent substrates. Theadsorbent media can alternatively be configured relative to theplurality of microreactors as a contiguous thin film over a singlesubstrate, with the reactor effluent from each microreactor passingover, around or through different spatially addressable portions of thatsingle film. Preferably, however, the reactor effluent stream of theplurality of microreactors is simultaneously passed over a plurality ofindividually addressable adsorbent media, each of which is located on anisolated region that spatially corresponds to a particular microreactor.The particular configuration for the adsorbent media is not limiting,and can include films, packed wells, porous (flow-through) adsorbents,and microparticles (generally analogous to the many configurationoptions for the candidate material—reference FIG. 3A through FIG. 5).Referring now to FIG. 15A, for example, an adsorbent-material array 700comprises an adsorbent material 720 on various regions of a substrate710. The various regions are preferably delineated by wells (indicatedgenerally as 730) that can be formed in the substrate 710 usingmicrofabrication techniques known in the art. The adsorbent material 720is preferably the same at each region, but could be a differentadsorbent material at two or more different regions. Temperature controlfor the adsorption (and subsequently for desorption) can be achieved,for example by use of a temperature-control block 400 (FIG. 15B). Thetemperature of each of the adsorbent-material regions can be controlledto be the same or varied (e.g., in a temperature gradient), and can becontrolled collectively as shown, for example, in FIG. 15B, orindividually as shown, for example, in FIG. 15C (e.g., with individualmicroscale resistive heating elements 410 integral with thetemperature-control block 400). The amount and/or thickness of theadsorbent material should be suitable for the separation application towhich it is directed. Typically, such adsorbent materials 720 can beformed as a film or deposited into a well on the substrate 710, and thefilm or well-deposited adsorbent can have an average thickness rangingfrom about 5 μm to about 15 mm, preferably from about 10 μm to about 5min, and more preferably ranging from about 50 μm to about 1 mm.Approaches for forming such adsorbent materials and/or depositing themon a substrate as a film or in a well are known in the art. In anexemplary approach, an adsorbent material (e.g., silica gel) can beformed on a substrate as taught in copending U.S. patent applicationSer. No. 09/149,586, filed Sep. 8, 1998 by Desrosiers et al. Indicatorreagents or other imaging agents can, where appropriate for theparticular chemistry involved, be pre-dispersed within the adsorbent.The amount of adsorbent material deposited on a particular portion ofthe adsorbent array 700 is not limiting, and will vary depending uponthe required surface area and the required sorbent mass, each of whichwill, in turn, vary depending upon the chemical reaction of interest andthe geometry of the array 700. While the adsorbent materials arepreferably formed on a plurality of regions that are coplanar with eachother, alternative, non-planar geometries can also be employed.

In a preferred configuration, the adsorbent materials are spatiallyseparated at an exposed surface of the substrate, and arranged such thatthe array of adsorbent materials can be integrated with the chemicalprocessing microsystem to efficiently access each of the plurality ofreactor effluents from each of the microreactors. As such, the number ofdifferent regions of an adsorbent material on an array preferablycorresponds to the number of microreactors in the chemical processingmicrosystem. Specifically, the number of adsorbent-material containingregions on an adsorbent array can be one for a single microreactor, butis more typically at least 2, preferably at least 4 or at least 5, morepreferably at least 10, still more preferably at least 25, even morepreferably at least 50, yet more preferably at least 100, and mostpreferably at least 250. Present microscale and nanoscale fabricationtechniques can be used, however, to prepare adsorbent arrays having aneven greater number of different adsorbent-material-containing regions.For higher throughput operations, for example, the number of regionshaving adsorbent materials can be at least about 1000, more preferablyat least about 10,000, even more preferably at least about 100,000, andmost preferably at least about 1,000,000 or more. The separation ofadsorbent-material-containing regions on the substrate, as well theplanar density thereof, can likewise correspond to the separation andplanar density of the microreactors and candidate-material arrays, asset forth above. Specifically, the separation between adjacent regionsof adsorbent material can range from about 50 μm to about 1 cm, morepreferably from about 100 μm to about 7 mm, and most preferably fromabout 1 mm to about 5 mm. The inter-region spacings can be not more thanabout 1 cm, not more than about 7 mm, not more than about 5 mm, not morethan about 4 mm, not more than about 2 mm, not more 1 mm, not more thanabout 100 μm, and not more than about 50 μm. Exemplary inter-regionsspacings (center-to-center) based on preferred embodiments of theinvention are 4 mm for having 256 addressable regions on a three-inchwafer substrate, and 2 mm for having 1024 addressable regions on athree-inch wafer substrate. As such, the surface density of discreteadsorbent material regions can range from about 1 region/cm² to about200 regions/cm², more preferably from about 5 regions/cm² to about 100regions/cm², and most preferably from about 10 regions/cm² to about 50regions/cm². The planar density can be at least 1 region/cm², at least 5regions/cm², at least 10 regions/cm², at least 25 regions/cm², at 50regions/cm², at least 100 regions/cm², and at least 200 regions/cm². Forsome reactions, lower or mid-range densities may be preferred. For otherreactions, higher densities may be suitable. Additionally, even higherdensities may be achieved as fabrication technology develops tonano-scale applications. As discussed below, the arrangement of theplurality of adsorbent materials (including separation and relativespatial address) and the plurality of regions should be correlated withthe arrangement of microreactors for integration therewith.

In one embodiment, the array of material consists of, or alternatively,consists essentially of, a substrate and adsorbent materials at separateportions of the substrate. Preferably, the array of adsorbent materialsconsists essentially of the substrate and the adsorbent at the pluralityof adsorbent-containing regions. As used in this context, the phrase“consists essentially of” is intended to exclude other microcomponentssuch as microreactors, valves, active mixers, fluid supply manifolds,etc, without excluding structure whose function is merely to hold anadsorbent material in a particular position or to confine an adsorbentmaterial to a particular space. For example, the adsorbent materialcould be provided as microparticles using frits to hold suchmicroparticles in place. In such instances, if the adsorbent array doesnot contain other microcomponents, the array is still considered to“consist essentially of” the substrate and adsorbent.

In a preferred embodiment, an array of adsorbent materials, such assilica gel, are deposited onto a substantially planar substrate having aplurality of substantially co-planar wells formed at one surface of thesubstrate. With reference to FIG. 16A and 16B, an adsorbent array 700comprises 256 circular-shaped wells 730 arranged in a sixteen-well bysixteen-well square array, with each well having a diameter of about1.25 mm and a depth of about 0.1 mm. The distance between wells is about4 mm. The preferred well-containing substrate 110 can be formed, forexample, using photolithographic microfabrication techniques known inthe art. The adsorbent material(s) can then be deposited in each of thewells to form the adsorbent containing array 700. In an alternativelypreferred embodiment, the adsorbent array comprises adsorbentmaterial(s) on up to 1024 regions of a substrate having 1024 wellsarranged in a 32-well by 32-well square array. Such an adsorbent arraycan be prepared, for example, as described above in connection with the256-well array, except that the distance between wells is reduced toabout 2 mm.

As noted, the array of adsorbent materials is preferably integrated withthe chemical processing microsystem. The adsorbent materials can beintegrated directly with the microreactors, for example, as shown inFIGS. 17A and 17B. Briefly, the adsorbent array 700 can be integral withthe microreactors such that a first surface 701 of the adsorbent array700, together with an exposed surface of the adsorbent material 720 canform a portion of the surface that defines the reaction cavity. (FIG.17A, FIG. 17B). The candidate materials 120 and adsorbent materials 720can be formed on different substrates 110, 710 and both exposed to thereaction cavity (FIG. 17A), or can, alternatively, be formed on opposingsurfaces of the same substrate 110/710 with the candidate material 120exposed to the reaction cavity and the adsorbent material 720 exposed toa separate separation cavity, with fluid communication between thereaction cavity and the separation cavity (FIG. 17B). These approachesare generally suitable when the adsorbent materials and the substrateare inert with respect to the chemical process of interest, are inertwith respect to the candidate materials being screened, and arecompatible with the reaction conditions employed to effect the chemicalprocess of interest.

More preferably, however, the adsorbent materials are integrated withthe chemical processing microsystem independent of, and withoutaffecting the structural integrity of, the microreactors and/ormicrocomponents thereof. With reference to FIG. 1C, the modular,structurally independent design of the array of adsorbent materials,allows the adsorbent array 700 to be efficiently loaded to the chemicalprocessing microsystem 10, contacted with the reactor effluent streamand subsequently unloaded from the chemical processing microsystem 10.The microsystem 10 can then, if desired, be reloaded with anotheradsorbent array 700′. Hence, the adsorbent array 700 is preferablyinterchangeable with the chemical processing microsystem withoutaffecting the structural integrity of the microreactors and/or fluidsupply manifold, fluid distribution manifold, heat transfer components,etc.

Referring to FIG. 18A, in a most preferred embodiment, a chemicalprocessing microsystem 10 comprises a plurality of microreactors 600formed in a plurality of laminae that include an interchangeablecandidate-material array 100 and, integral therewith, a plurality ofmicroseparators 900 formed in a plurality of laminae that include aninterchangeable adsorbent array 700. The microreactor 600 issubstantially the same as that shown in FIG. 8 and described inconnection therewith. (As shown in FIG. 18A, however, the microreactor600 is inverted relative to as shown in FIG. 8.) A microseparator 900 isformed in a plurality of laminae comprising an (adsorbent-containing)first laminate 700, and a composite separator block 800 comprising a(separator) second laminate 820 adjacent to the adsorbent-containingfirst laminate 700 and a (capping) third laminate 830 adjacent theseparator second laminate 820. A releasable seal 300 is preferablysituated between the adsorbent-containing first laminate 700 and theseparator second laminate 220.

More specifically, with reference to FIG. 18A, the adsorbent-containingfirst laminate 700 has a first surface 701, a second surface 702 inspaced, substantially parallel relationship to the first surface 701,and a circumferential edge 703. The separator second laminate 820 has afirst surface 821 in releasable contact with the second surface 702 ofthe first laminate 700, a second surface 822 in spaced, substantiallyparallel relationship to the first surface 821, and a circumferentialedge 823. The capping third laminate 830 has a first surface 831 bondedto the second surface 822 of the separator second laminate 820, a secondsurface 832 in spaced, substantially parallel relationship to the firstsurface 831, and a circumferential edge 833. The separator secondlaminate 820 further comprises interior edges 824 and interior surface825 defining an aperture (with corresponding void space) in the secondlaminate 820, such that, taken together, the second and third laminates820, 830 form a composite substructure, separator block 800, comprisinga well defined by the interior edge 824 and interior surface 825 of thesecond laminate 820 and those portions of the first surface 831 of thethird laminate 830 circumscribed by such interior edge 824. Theadsorbent-containing laminate 700 is preferably releasably engaged withat least one of the adjacent laminates, and preferably, with at leastthe separator block 800. The releasable contact between the separatorsecond laminate 820 and the adsorbent-containing first laminate 700 ispreferably provided by a releasable seal 300 such as a gasket or othersuitable releasable-sealing means. The adsorbent-containing laminate 700is also preferably in releasable contact with (and releasably engagedwith) a surface of any other adjacent laminate, such as thetemperature-control block 400.

The adsorbent-containing laminate 700 further comprises an adsorbentmaterial 720 effective for separating at least one component of thereactor effluent stream (e.g., reaction product or unreacted reactants).The candidate material 720 can be formed on an exposed surface of thefirst laminate 700—as shown in FIG. 18A, on a surface 712 of a wellformed in the adsorbent-containing first laminate 700. The well in theadsorbent-containing laminate is defined by material-containing surface712, interior edges 714 and interior surface 715. Taken together, thefirst, second and third laminates 700, 820, 830 form a microseparatorseparation cavity defined by the interior edges 824 and interior surface825 of the second laminate, by the interior edges 714, interior surface715, adsorbent-containing surface 712 and the adsorbent material 720 ofthe first laminate 700, and by those portions of the third laminate 830circumscribed by the interior edges 824 of the second laminate 820.

For fluid distribution within the chemical processing microsystem 10,the microreactor 600 comprises a reactor inlet 250 formed as amicrofluidic channel 251 between the second and third laminates 220,230, and a reactor outlet port 260 formed as the terminal portion of amicroreactor outlet channel 261 having an interior surface defining anaperture in the third laminate 230. The inlet 250 is preferably in fluidcommunication with a microfluidic supply manifold, such as that shown inFIG. 7B and described in connection therewith (with the microfluidicchannel 251 of FIG. 18A corresponding to a terminal channel section 517of FIG. 7B). The microreactor outlet port 260 is in fluid communicationwith the separator inlet port 850 by means of microreactor outletchannel 261, connecting channel 550, and separator inlet channel 851.The connecting channel 550 can be of any suitable geometry (e.g., shapeand/or length) to facilitate communication between each of the pluralityof microreactors 600 and each of the plurality of correspondingmicroseparators 900. The separator inlet port 850 is in fluidcommunication with the separation cavity for supplying the reactoreffluent stream to the microseparator. Inlet port 850 is formed as theterminal portion of the microseparator inlet channel 261 having aninterior surface defining an aperture in the third laminate 830. Theseparator outlet port 860 is in fluid communication with the separationcavity and is formed as the terminal portion of a microfluidic separatoroutlet channel 861. The outlet channel 861 can be formed as amicrofluidic channel between the second and third laminates 820, 830.The microseparator outlet channel 861 is preferably in fluidcommunication with a microfluidic discharge manifold, such as that shownin FIG. 14 and described in connection therewith (with the microfluidicoutlet channel 861 of FIG. 18A corresponding to a terminal channelsection 517 of FIG. 14).

The microseparator, such as that shown in FIG. 18A, may further compriseone or more ports (not shown) for analytical microinstruments (e.g.,temperature and/or pressure monitoring) and/or for process controlelements (e.g., pressure-relief valves). The microseparator may alsocomprise one or more temperature-control blocks 400, 400′. Thetemperature-control blocks 400, 400′ can be a cooling block, a heatingblock or an insulator. As discussed above, the temperature of thetemperature-control blocks can be controlled to maintain the sametemperature for the plurality of microreactors, or alternatively, toprovide a different temperature a plurality of microreactors. Moreover,control of the temperature can be collective and or individual to eachmicroseparator. The temperature control block 400 associated with themicroreactors is as described above in connection with FIG. 8. Thetemperature-control block 400 associated with the microseparators can beemployed as a cooling-block during adsorption of components from thereactor effluent stream, and subsequently, after removal ofadsorbent-containing laminate 700 with adjacent temperature-controlblock 400, as a heating-block to facilitate desorption therefrom.Because, in many applications, the reaction temperature can differ fromthe adsorption temperature substantially—up to and, for some reactions,in excess of several hundred degrees Celsius—it may be preferred toprovide for independent temperature control of the microreactors and themicroseparators. In one approach for such independent temperaturecontrol, the microreactors 600 and the microseparators 900 haveindependently-controlled temperature-control blocks 400 associatedtherewith. These subsystems can be thermally isolated from each other bytemperature control block 400′, situated between and in releasablecontact with the composite separator block 800 and the composite reactorblock 200. The temperature control block 400′ is preferably a coolingblock or an insulator block suitable, for example, to provide for orallow for cooling of the reactor effluent stream as it passes throughthe connecting channel 550 and before it reaches the separation cavity,such that the temperature suitable for selective adsorption onto theadsorbent material 720 can be independently controlled from the reactiontemperature.

A plurality of microseparators, such as the preferred embodiment shownin FIG. 18A, can be fabricated in a plurality of laminae usingmicroscale and nanoscale fabrication techniques known in the art. Theparticular details of such fabrication are, in large part, analogous asdescribed above for fabrication of the microreactors 600. For example,the separator block 800 can be fabricated in a manner analogous to themethods disclosed with reference to FIGS. 9 and 10.

In operation, with reference to FIGS. 18A, one or more reactants 20 aresimultaneously supplied to a plurality of microreactors 600 through asupply distribution manifold and supply inlet channel 251 and inlet port250. The one or more reactants 20 are preferably diffusion-mixed in thereaction cavity and simultaneously contacted with each of the candidatematerials 120 under process conditions conducive to (or intended to, forresearch purposes) effect the chemical reaction of interest in eachmicroreactor 600 to form one or more reaction products 30. The reactionproducts 30, as well as any unreacted reactants 20, are discharged fromeach reaction cavity through each microreactor outlet port 260 anddischarge channel 261 as reactor effluent streams 40. The reactoreffluent streams 40 are cooled as they pass through the connectingchannel 550, and are then simultaneously supplied to the plurality ofmicroseparators 900 through separator inlet channel 851 and inlet port850. The reactor effluent stream 40 is resident in the separator cavityand in contact with adsorbent material 720 for a period of timesufficient to simultaneously adsorb a quantitatively detectable amountof at least one analyte component (e.g., reaction product or unreactedreactant) of the reactor effluent stream 40. Such separator residencetimes will vary with the chemistry involved, but can typically rangefrom about 1 μsec to about 1 hr, preferably from about 100 μsec to about30 minutes, more preferably from about 1 msec to about 15 minutes, andmost preferably from about 10 msec to about 2 minutes. The separatedeffluent stream 50 is then simultaneously discharged from the separationcavity through separator outlet port 260 and outlet channel 261 andthrough a discharge manifold.

Although it is generally preferred (as shown in FIG. 18A) that theplurality of microreactors 600 are formed in a first plurality oflaminae 100, 200, 300 and that the plurality of microseparators 900 areformed in a second, independent plurality of laminae 700, 300, 800,these microcomponents can, in an alternative embodiment, be formed in acommon plurality of laminae. With reference to FIGS. 7G, for example, anarray of thirty-two microreactors 600 and thirty-two microseparators 900are formed in a common plurality of laminae to be substantially coplanarwith each other. FIG. 7H shows an array of 128 microreactors 600 and 128microseparators 900 formed in a common plurality of laminae to besubstantially coplanar with each other. The plurality of laminae can, ineither case, be substantially as shown in FIG. 8, except that candidatematerial 120 (FIG. 8) will be included in the microreactors 600, whereasan adsorbent material 720 (FIG. 18A) will be included in themicroseparators 900. Referring now to both FIGS. 7G and 7H, reactantsare supplied to the plurality of microreactors 600 and the reactoreffluent is discharged therefrom as described above. The reactoreffluent is then communicated to the plurality of microseparators 900 byconnecting channels 550. The separated reactor effluent stream can bedischarged through outlet channels 861, common outlet headers 862 andcommon outlet port 863.

An alternative embodiment, shown in FIG. 18J, is directed toward a“flow-through” reaction system (e.g., analogous to a plug-flow reactor).Briefly, the microprocessing system 10 comprises a plurality ofmicroreactors 600 formed in one or more laminae 100. Thematerial-containing laminate 100 comprises a candidate material 920 suchas beads or particulates contained within the microreactors by a porousbarrier 126 (e.g., frits, porous plug, etc., as described above). Asshown, the plurality of microreactors 600 are sealed and heated byadjacent temperature control blocks—shown as adjacent heaters 980—withreleasable seals 300 (e.g., gaskets) situated between the heaters 980and the microreactor laminae 100. Reactants 20 are provided to themicroreactors 600 through an inlet distribution manifold 500 in fluidcommunication with the micoreactors 600 via connecting channels 550. Thedistribution manifold 500 is thermally isolated from the microreactors600 by temperature control block 400. After contacting the candidatematerials (e.g., catalysts) 920 under reaction conditions, reactoreffluent 60 is passed through connection channels 550 to a dischargemanifold 501, and further to an external distribution (waste) system.The discharge manifold 501 is likewise thermally insulated from themicroreactors 600 by another temperature control block 400. Evaluationof the candidate materials can be determined by analysis of reactionproducts, for example, by sampling of the reactor effluent stream usingone or more sampling probes 910 (e.g. sampling needles) that are inselective fluid communication with one or more of the microreactors 600,and in further fluid communication with a detection system (e.g., gaschromatograph, mass spectrometer, FTIR, etc.). A septum or othersuitable accessible barrier 911 may be employed in connection with thesampling system.

FIG. 18B shows a perspective view of a partially-assembled housing 214adaptable for assembly and operation of a modular chemical processingmicrosystem 10 as shown in FIG. 18A and discussed in connectiontherewith. As shown in FIG. 18B, the partially-assembled housingcomprises a first and second microreactor support block 217, 217′,respectively, and a first and second microseparator support block 219,219′, respectively. The first microreactor support block 217 has amicroreactor staging area 601 adapted to receive thecandidate-material-containing laminate (100 of FIG. 18A) oralternatively, a plurality of laminae (100, 200, 300 of FIG. 18A) thatcomprise the plurality of candidate-material-loaded microreactors (600of FIG. 18A). Likewise, the first microseparator support block 219 has amicroseparator staging area 901 adapted to receive theadsorbent-containing laminate (700 of FIG. 18A) or, alternatively, aplurality of laminae (700, 300, 800 of FIG. 18A) that comprise theplurality of adsorbent-loaded microseparators (600 of FIG. 18A).Temperature control blocks (400 of FIG. 18A) can be provided to thehousing 214 with the plurality of microreactor laminae and/or theplurality of microseparator laminae, or can be made integral with thesecond microreactor support block 217′ and/or the first microseparatorsupport block 219. A central support block 218 can be situated betweenthe first surface of the microreactor support block 217 and the secondsurface of the microseparator support block 219′, and can compriseanother temperature-control block (400′ of FIG. 18A)—such as amachinable glass ceramic insulation material (e.g. MACOR) or quartz,that provides connecting channels (550 of FIG. 18A) between themicroreactors (600 of FIG. 18A) and microseparators (900 of FIG. 18A).The plurality of laminae in which the microreactors 600 andmicroseparators 900 are formed can be held together by compressivefastener fittings 216 that can be joined by bolted connection throughapertures aligned as indicated by dashed lines. Other compressivefasteners—for example, axially-aligned springs, spring clamps orhydraulics could likewise be employed.

FIGS. 18C and 18D show a perspective view and corresponding sectionalview (taken at A-A), respectively, of another preferred,partially-assembled housing 214 adaptable for assembly and operation ofa modular chemical processing microsystem 10 as shown in FIG. 18A anddiscussed in connection therewith. As shown in FIGS. 18C and 18D, thepartially-assembled housing comprises first and second microreactorsupport blocks 217, 217′, respectively. The first microreactor supportblock 217 has a microreactor staging area 601 adapted to receive acandidate material containing laminate (candidate material array) 100(with the candidate materials facing upward for the orientation shown inFIGS. 18C and 18D). The microreactor staging area 601 is preferably avoid space in the first microreactor support block 217 into which, asdiscussed below, the candidate material array 100 will be inserted uponassembly of the system. As such, upon assembly, the first microreactorsupport block 217 provides lateral (radial) support to the candidatematerial array 100. In addition to its support function, the firstmicroreactor support block 217 can also have other functional features,including a temperature control function and a subassembly-clampingfunction, each of which is discussed below in connection with FIGS. 18Eand 18G, respectively. The second microreactor support block 217′likewise has a microreactor staging area 601′ adapted to receive thecandidate material containing laminate (candidate material array) 100.The microteactor staging area 601′ is preferably a raised platform on orintegral with the second microreactor support block 217′ onto which, asshown and as further discussed below, the candidate material array 100can be situated upon assembly of the system. As such, upon assembly, thesecond microreactor support block 217′ provides normal (vertical)support to the candidate material array 100. In addition to its supportfunction, the second microreactor support block 217′ can also have otherfunctional features, including a temperature control function asdiscussed below. Referring further to FIGS. 18C and 18D, thepartially-assembled housing also comprises first and secondmicroseparator support blocks 219, 219′, respectively. The firstmicroseparator support block 219 has a microseparator staging area 901adapted to receive a the adsorbent-containing laminate (adsorbent array)700 (with the adsorbent materials facing downward for the orientationshown in FIGS. 18C and 18D). The microseparator staging area 901 ispreferably a void space in the first microseparator support block 219into which, as discussed below, the adsorbent array 700 will be insertedupon assembly of the system. Hence, upon assembly, the firstmicroseparator support block 219 provides lateral (radial) support tothe adsorbent array 700. In addition to its support function, however,the first microseparator support block 219 can also have otherfunctional features, including a temperature control function, discussedbelow, and a subassembly-clamping function, discussed below inconnection with FIGS. 18G. The second microseparator support block 219′likewise has a microseparator staging area 901′ adapted to engage theadsorbent-containing laminate (adsorbent array) 700. The microseparatorstaging area 901′ is preferably a raised platform on or integral withthe second microseparator support block 219′ against which, as shown andas further discussed below, the adsorbent array 700 can be situated uponassembly of the system. The second microseparator support block 219′,therefore provides normal (vertical) support to the adsorbent array 700once the system is assembled. In addition to its support function, thesecond microseparator support block 219′ can also have other functionalfeatures, including a temperature control function as discussed below.

Upon engagement of the first and second microreactor support blocks 217,217′, the candidate material-containing laminate (candidate materialarray) 100 is brought into contact with the reactor block 200 (See alsoFIG. 18A). The reactor block 200 includes a reactant supply manifoldintegral therewith (shown as 500 and described in connection with FIGS.7B and 7I) having a single common inlet port (510 of FIG. 71) near theedge of the manifold (500 of FIG. 7I), and having an elbow-shapedvertical conduit 508 extending normal to the reactor block 200 forinterfacing with an external fluid distribution (reactant supply) system(480 of FIG. 1C). A releasable seal (e.g. graphite gasket) (300 of FIG.18A) is preferably situated between the reactor block 200 and thecandidate material array 100. Likewise, upon engagement of the first andsecond microseparator support blocks 219, 219′, the adsorbent-containinglaminate (adsorbent array) 700 is brought into contact with theseparator block 800 (See also FIG. 18A). The separator block 800includes an effluent discharge manifold integral therewith (shown as 501and described in connection with FIG. 14) having a single common outletport near the edge of the manifold, and having an elbow-shaped verticalconduit 508 extending normal to the separator block 800 for interfacingwith an external fluid distribution (effluent discharge) system. Areleasable seal (e.g., graphite gasket) (300 of FIG. 18A) is preferablysituated between the separator block 800 and the adsorbent array 700. Atemperature control block 400′, comprising one or more insulator blocks,is situated between the reactor block 200 and the separator block 800.The temperature control block 400′ also comprises a number of connectingchannels (550 of FIG. 18A) providing fluid communication between theoutlet port (260 of FIG. 18A) of the reactor block 200 and the inletport (850 of FIG. 18A) of the separator block 800.

Engagement and disengagement of first and second microreactor supportblocks 217, 217′, and independently, the first and second microseparatorsupport blocks 219, 219′ is preferably supplied using one or morehydraulic mechanisms. Such engagement and disengagement can preferablybe effected independently for the microreactor support blocks 217, 217′versus the microreactor support blocks 219, 219′, such thatcandidate-material arrays 100 and adsorbent arrays 700 can be loadedand/or unloaded from the microsystem independently of each other. In apreferred embodiment shown in FIGS. 18C and 18D, hydraulic chambers 950(e.g., Mead Fluid Dynamics) provide a vertically-oriented hydraulicforce (e.g., ˜40 psi) and are coupled by shafts 956 to flanges 952, tosupport plates 954, 955, and/or directly to the second microreactorsupport block 217′ or the second microseparator support block 219′. Theperiphery of support plates 954, 955, respectively, are furthersupported by support brackets 958 that are slidably coupled to guideposts 959 such that upon hydraulically-actuated motion of shafts 956,the second microreactor support block 217′ or the second microseparatorsupport block 219′ will move vertically. An additional, central supportplate 960 can support the fluid distribution subassembly 970 thatcomprises the first microreactor support block 217, reactor block 200,temperature control block 400′, separator block 800, and firstmicroseparator support block 219, together with required releasableseals (300 of FIG. 18A). The central support plate 960 can be furthersupported along its periphery by central support brackets 962. Thecentral support brackets 962 can be slidably coupled to guide posts 959,or alternatively, permanently or adjustably secured to guide posts 959(e.g., with a set screw (not shown)). In a preferred design, the centralsupport brackets 962 are slidably coupled to guide posts 959 with alimited range of motion defined by guide springs 964 (shown only in FIG.18D). Significantly, guide springs 964 allow for either end of themicroprocessing system 10—that is, either the microreactor end (lowerportion as shown in FIG. 18C and 18D) or the microseparator end (upperportion as shown in FIGS. 18C and 18D)—to be engaged and disengagedindependently from each other, thereby providing for great flexibilitywith respect to loading and/or unloading of candidate-material arrays100 and adsrobent arrays 700. In addition to a support function, thecentral support plate 962, as well as the other support plates 954, 955,can have other functionalities such as temperature controlfunctionality, as discussed below.

Temperature control of the microreactors and microseparators areeffected using active (e.g., heaters) and passive (e.g., insulation)temperature control elements, together with temperature control systems.As noted, various aspects of temperature control elements are integratedinto some of the aforementioned components. Referring to FIGS. 18C and18D, the microreactors (600 FIG. 18A) and candidate material array 100can be heated to a reaction temperature of interest by a heater 980 inthermal communication with the candidate-material array 100. The heater980 can be a resistive heater, and is preferably a “pancake-type”resistive heater (e.g.,˜1200 W). As shown, heat energy from the heater980 is transferred by conduction through the second microreactor supportblock 217′ to the candidate-material array 100. In such an embodiment,the second microreactor support block 217′ is preferably a materialhaving a high thermal conductivity (e.g., copper). Temperature controlblock (insulator block) 400 is situated under the heater 980 to minimizeheat loss in a direction away from the microreactors. The resistiveheater 980 can also be zoned to provide a temperature gradient acrossthe various microreactors. Additional, fine temperature control can beprovided to the microreactors by smaller, controllably resistive heaters982 a, 982 b, placed, for example, in the periphery of the firstmicroreactor support block 217. With reference to FIG. 18E, in oneembodiment, one or more active temperature control elements such asresistive heaters 982 a, 982 b (˜25 W) can be integral with the firstmicroreactor support block 217, and as shown, situated in one or moreheater cavities 984 a, 984 b, 984 c, 984 d, 984 e, 984 f formed therein.Each of such resistive heaters 982 a, 982 b can be held in place withset screws 986 a, 986 b, respectively and can be selectively controlledwith a temperature control system connected to the resistive heaters 982a, 982 b via control wires 983 a, 983 b, respectively, to providefine-temperature control for the microreactors. The temperature controlsystem can also include thermocouples 988 a, 988 b. Although resistiveheaters 980, 982 a, 982 b, etc. are described in connection with thisembodiment, other types of appropriate heaters (e.g., thermoelectricheaters, fluid heat-exchangers) can also be employed. With furtherreference to FIGS. 18C and 18D, the microseparators (900 of FIG. 18A)and adsorbent-material array 700 can be cooled to a temperatureappropriate for selective adsorption of the one or more analytes (e.g.,reaction products or unreacted reactants) of interest by a cooler inthermal communication with the adsorbent array 700. The cooler can be afluid heat-exchanger in fluid communication with a cold-temperature heatsink. As shown, heat energy from the adsorbent array 700 is transferredby conduction through the second microseparator support block 219′ tocooling channels 990 formed therein. A cooling fluid is circulatedthrough the cooling channels 990 to an external heat sink. In such anembodiment, the second microseparator support block 219′ is preferably amachinable material having a high thermal conductivity (e.g., aluminum). Temperature control block (insulator block) 400 is situated over thecooler of the second microseparator support block 219′ to minimizecooling of components situated in a direction away from themicroseparators. The cooling channels can be “zoned”—for example withseparate channels to separate heat sinks, as desired, to achieve atemperature gradient across the microseparators. Additional, finetemperature control can be provided in the first microseparator supportblock 219 in a manner similar to that described above in connection withthe first miroreactor support block 217, except that thermoelectriccoolers could be employed rather than resistive heaters 982 a, 982 b.The cooler can be integrated with a temperature control system that canalso include thermocouples, for example, integral with the firstseparator support block 219. As shown, further temperature control ofthe microseparators is provided by an additional fluid heat-exchangertype cooling system that includes cooling channels 992 formed in thecentral support plate 960 through which a cooling fluid can flow. Heatenergy from the microseparators can be transferred, by conduction,through the adsorbent array 700, the first microseparator support block219, and the central support plate 960 to the cooling fluid, andultimately to an external heat sink. Although fluid heat-exchanger typecoolers are described in connection with this embodiment, other types ofappropriate coolers (e.g., thermoelectric coolers, refrigerants) canalso be employed.

Temperature control of the fluid distribution subassembly 970 ispreferably provided by a temperature control block 400′ (such as apassive insulator block 400′). With reference to FIGS. 18G and 18H, thetemperature control block can be fabricated from a plurality of thinner(e.g., 0.5 inch or smaller) individual temperature control blocks 400′,interfaced with releasable seals 300, to facilitate fabrication of theconnection channels (550 of FIG. 18A). An insulating shield 996encircling the temperature control block 400′ can provide additionalpassive temperature control.

With reference to FIGS. 18F through 18H, the fluid distributionsubassembly 970 (comprising the first microreactor support block 217,reactor block 200, one or more temperature control blocks 400′,separator block 800, and first microseparator support block 219,together with releasable seals 300) can be preassembled prior to use inconnection with the microsystem of FIGS. 18C and 18D. Allignment of thecomponents of the fluid distribution subassembly 970 is preferablyprovided by allignment pins 972 inserted through precision-machinedallignment apertures 974. Threaded fasteners (not shown) extendingbetween and connecting the first microreactor support block 217 and thefirst microseparator support block 219 can be used to secure thesubassembly, with the support blocks 217, 219 acting as clamping platesand providing a support function.

The fluid distribution subassembly 970 can be interfaced with one ormore external fluid distribution subassemblies 920, as shown in FIG.18F. Reactants and reactor effluent (or separated reactor effluentstreams following adsorption) can be supplied to the microreactors ordischarged from the microseparators, respectively, through one or moresuch external fluid distribution subassemblies 920 (shown only for theeffluent/discharge side). Briefly, with further reference to FIGS. 18Gand 18H, a reactant can pass through an external fluid distributionsubassembly (not shown for reactant/inlet side) into a reactantsupply-side elbow-shaped vertical conduit 508 extending normal to thereactor block 200, through the reactant supply manifold integral withthe reactor block 200 and into the microreactors. After reactiontherein, the reactor effluent passes through the connecting channels(550 of FIG. 18A) of the temperature control block 400′ and into themicroseparators where one or more components thereof can be separated.The separated effluent stream then passes through the dischargemannifold integral with the separator block 800 and is discharged fromthe microsystem through the discharge-side elbow-shaped vertical conduit508 extending normal to the separator block 800. Discharge-side conduit508 is in fluid communication with the external fluid distributionsubassembly 920. With reference to FIG. 18I, the separated reactoreffluent stream passes from the discharge-side conduit 508 (e.g., glass)through an elbow 922 (e.g., glass), through a flexible microcapillary924 (e.g., polyimide-coated quartz capillary), through a rigid, largerdiameter transfer conduit 926 and finally through the outlet port 922 ofsubassembly 920 to the external fluid distribution system (e.g., waste).Fittings, adhesives, bonding, etc. known in the art can be used toeffect appropriate connections of the various distribution components508, 922, 924, 926.

After one or more of the components of the reactor effluent stream havebeen separated therefrom (e.g., by adsorption onto the adsorbingmaterial), the separated component may be detected (e.g., as to itspresence or absence) and/or quantitatively determined using a variety oftechniques known in the art. As noted, such determination can beeffected in situ in the chemical processing microsystem. Alternativelyand preferably, however, such determination is effected at a subsequenttime and at a remote location.

Quantitative determination of reactor effluent components can beperformed, for example, by desorbing such components from the adsorbentmaterial (e.g., by heating), and then detecting the desorbed componentby gas chromatography, mass spectroscopy, infrared spectroscopy, opticalspectroscopy (e.g., with indicator imaging) or other suitable approach.Briefly, for example, in the thermal desorption approach, samples can bedesorbed into a gas chromatograph or into a mass spectrometer andanalyzed as known in the art. Preferred gas chromatography approachesinclude rapid GC protocols such as those disclosed in Cooke, DecreasingGas Chromatography Analysis Times using a Multicapillary Column, Abs.403P, Book of Abstracts, PittCon '96 (1996). Infrared spectroscopy canbe applied by desorbing the adsorbates into a standard gas cell in anFTIR spectrometer. With reference to FIGS. 19A through 19C, for example,a detection probe 910 can be positioned over an adsorbent-containingregion of an adsorbent array 700, and the reactor effluent component canbe desorbed therefrom by heating. The heating can be controlledindividually for each region (FIG. 19A, FIG. 19C) using, for example,spatially addressable resistive heating elements 410 within atemperature-control block 400 (FIG. 19A) or spatially addressable lasersource 420 (FIG. 19C). The heating can alternatively be appliedcollectively and simultaneously to each of the adsorbent-containingregions to desorb reactor effluent components from each regionsimultaneously, but using multiple detector probes 910 in parallel.

In another detection approach involving indicator imaging (e.g.colorimetry)/spectroscopy the array of adsorbed materials can be exposedto detection agents (e.g., indicating agents such as fluorescent tags,dyes, colorants, radionuclides, biological markers or tags, etc.) thatare selective for an analyte (e.g., one or more particular reactoreffluent components of interest). Typically, the detection agent reactsand/or interacts (e.g., through hydrogen bonding) with one or more ofthe adsorbed species to form a detectable species. The array is thenimaged to detect the detectable species using, for example, suitablespectroscopic techniques to determine fluorescent intensity or colorwavelength and correlating the same with known standards to determinethe presence, absence or quantity (relative or absolute) of the analytecomponent of interest. A preferred embodiment includes, with referenceto FIG. 1C, a station for applying a detection agent to the adsorbedspecies, and a detector. The station can be a spray station for sprayingdye or colorant onto the adsorbed component—or alternatively, forapplying a detection agent to the adsorbent material prior to thereaction. The spray station can have an automated XYZ translation stagefor providing relative motion between a stationary nozzle (e.g., apassive ultrasonic nozzle) and the array of adsorbent material.Detection agent can be provided to the spray nozzle from one or morereservoirs through feed lines by syringe-pump motive force. Nearsimultaneous detection can be determined, for example, by exposing thedetectable species to UV light, and determining intensity with parralleldetection devices, such as a CCD camera (e.g., Andor, Ireland) undersoftware control of the manufacturer. The CCD camera can detect UVfluorescence (e.g., for fluorescent dyes) and/or transmission absorbance(for color dyes). The detected signal can be correlated to signals fromknown standards to determine the presence, absence and/or absolute orrelative quantity of analyte.

FIGS. 16C and 16D show arrays of adsorbent materials that can beemployed in detection schemes involving thin-layer chromatography (TLC)techniques to determine the presence, absence or relative or absolutequantity of a particular reaction product of interest. FIG. 16C,including corresponding detail (taken at A), shows an array comprising aplurality of substantially parallel TLC channels, each of the pluralityof TLC channels 740 having one or more mobile-phase inlet ports 742 andone or more mobile-phase outlet ports 743 in fluid communication witheach other (via the TLC channel 740). The TLC channels 740, andmobile-phase inlet and outlet ports 742, 743 can be formed in asubstrate 710 using microfluidic manufacturing techniques generallyknown in the art, such as those discussed above in connection withfabrication of the microreactors, microseparators and fluid distributionsystems. The TLC channels 740 contain an adsorbent material 720 that issubstantially selective for one or more analytes (e.g., reactionproducts or unreacted reactant) of interest. The TLC channels 740 arearranged such that a portion of the adsorbent-material-containing TLCchannel 740, referred to herein as the adsorption spot 744, can be influid communication with a microseparator 900 of the invention (asdescribed above). The adsorption spot 744 can, in some embodiments, forma portion of a surface that defines the separation cavity (e.g., byhaving microseparator cavities arranged to correspond to the arrangementof adsorption spots 744 as shown in FIG. 16C). In preferred embodiments,the adsorption spot 744 is preferably located in a portion of the TLCchannel 740 that is closer to the mobile-phase inlet port 742 of the TLCchannel 740 than to the mobile-phase outlet port 743 thereof. Ingeneral, however, the length of TLC channel between the adsorption spot744 and the mobile-phase outlet port 743 is preferably sufficient toobtain meaningful TLC data upon subsequent elution of the adsorbedanalyte of interest. In operation, with reference to FIG. 16C and FIG.18A, an analyte in the reactor effluent stream 40 can be selectivelyadsorbed and deposited onto the adsorbent material 720 at the adsorptionspot 744 in the TLC channel 740, with the separated reactor effluent 60passing through the discharge manifold (501 of FIG. 14) as described.Following the reaction, the TLC-array 700 can be removed from themicroprocessing system 10 (as described), and then evaluated in a TLCdetection system (not shown) comprising a mobile-phase source, amobile-phase supply manifold (e.g., substantially as shown and describedin connection with FIGS. 7B or 7I), the TLC array 700, a mobile-phasedischarge mannifold (e.g., substantially as shown and described inconnection with FIGS. 14), a mobile-phase sink, together withappropriate releasable seals (e.g. gaskets) between the manifolds andthe TLC array 700. A TLC mobile phase (e.g., eluant or solvent) can flowin each of the plurality of mobile-phase inlet ports 742, through eachof the plurality of TLC channels 740, and out each of the plurality ofmobile-phase outlet ports 743. After optional treatment with appropriatedetection agents (e.g., indicating agents) and detection thereof, therelative movement of the analyte of interest down the length of the TLCchannel 740 can be correlated to known standards (included, for example,in the microreaction/microseparation system during the reaction ofinterest) for determination, and ultimately, for evaluation of thecandidate materials (or processing conditions, etc.). In anotherembodiment, shown in FIG. 16D, the microreactor effluent is dischargedfrom microreactors 600 through a discharge mannifold 501 (e.g., havingflow resistance characteristics substantially as described in connectionwith FIG. 14), and is contacted with an array of adsorbent-materialcontaining microseparators 900 arranged in one or more rows near theperipheral edge of the substrate. The microseparators can be on the samesubstrate as the microreactors 600, or alternatively, as shown in FIG.16E, on a different substrate, but in fluid communication with thedischarge flowpaths (e.g., through a row-of apertures 519 and connectingchannel 550 (not shown)). In either case, the microseparators can alsobe TLC channels 740 (with the adsorbent material situated therein)located along an external edge of the TLC array 700. An analyte can beselectively adsorbed onto the adsorbent material 720 in themicroseparators 900. The TLC-array 700 can be subsequently removed fromthe microprocessing system 10 (as described), and then evaluated in aTLC detection system (not shown) comprising a solvent with which theanalyte-containing edge of the adsorbent array 700 is contacted, andeluted therefrom (substantially as known in the art). After optionaltreatment with appropriate detection agents (e.g., indicating agents)and detection thereof, the relative movement of the analyte of interestcan be correlated to known standards, as discussed above.

The detection (following the desorption approach, the imaging approach,or otherwise) can be carried out for each of the plurality ofadsorbent-containing regions in rapid-serial fashion, in serial-parallelfashion (serial application for a subgroup of detectors) or incompletely parallel fashion. Significantly, even if serial desorptionand detection systems are applied herein, the results obtained representthe reaction components (e.g., reaction products) obtainedsimultaneously and concurrently from the plurality of microreactors. Assuch, the evaluation system of the invention offers a great degree offlexibility with respect to preservation and analysis of data.

While the preferred separation and analysis approach has beenexemplified herein with respect to an adsorption process, an analogousapproach can be taken based on other chemical separation techniques. Forexample, in place of the adsorbent material 720, a blank well 730 couldbe employed. The well 730 could be cryogenically cooled usingtemperature-control block 400 to facilitate condensation of gaseousreactor effluent components into the well 730. As another example, gaschromatographs and/or mass spectrometers can be used to “sniff” reactoreffluent, in rapid-serial and/or in parallel, directly and without firstadsobring the chemical species of interest. Note that while the methodsand embodiments of the invention can be exemplified primarily hereinfor, and preferably for, chemical reactions having gaseous reactionproducts, an analogous approach can be applied for evaluatingliquid-phase reactor effluent streams.

Removal of Candidate Materials from Microreactors

The plurality of different candidate materials being screened for theircapability to enhance the chemical process of interest can be removed,preferably simultaneously, from each of the plurality of microreactors.Specifically, a first candidate material is unloaded from a firstmicroreactor and, preferably simultaneously therewith, a secondcandidate material is unloaded from a second microreactor. If additionalcandidate materials were evaluated in additional microreactors, theneach additional candidate material is preferably likewise simultaneouslyunloaded from their respective individual microreactors.

In preferred embodiments, in which the candidate materials were suppliedto the plurality of microreactors as an array of candidate materials,the array can be removed from the chemical processing microsystem byreleasing the array from the other microreactor components (e.g., fluiddistribution system), and then withdrawing the released array. The arrayis preferably released without substantially affecting the structuralintegrity of the other microreactor components. With reference to FIG.2, for example, the candidate material array 100 can be released bydisengaging the first surface 201 of the reactor block 200 from thesecond surface 212 of the housing block 210. The array 100 can then beremoved by breaking the contact between the array 100, the seal 300 andthe heating block 400. An analogous approach can be taken for unloadingthe candidate material array 100 of FIGS. 8, 18A and 18B.

Significantly, once the array 200 is released and unloaded from theplurality of microreactors, a different candidate material-containingarray 100 can then be loaded to the microreactors. It may be desirable,in conjunction therewith, to provide a new, releasable seal 300 betweenthe adjacent surfaces of the array 100 and the reactor block 200.

Removal of Adsorbate-Containing Adsorbent from Microseparators

The adsorbate-containing adsorbent employed for separating one or morereactor effluent components can be removed, preferably simultaneously,from each of the plurality of microseparators. Specifically, a firstadsorbate-containing adsorbent is removed from a first microseparatorand, preferably simultaneously therewith, a second adsorbate-containingadsorbent is removed from a second microseparator. If additional reactoreffluent components were adsorbed from the reactor effluent streams ofadditional microreactors, then each additional adsorbate-containingadsorbent is preferably likewise simultaneously removed from theirrespective individual microseparators.

In preferred embodiments, in which the adsorbent is supplied to theplurality of microseparators as an array, the array can be removed fromthe chemical processing microsystem by releasing the array from theother microseparator components (e.g., fluid distribution system), andthen withdrawing the released array. The array is preferably releasedwithout substantially affecting the structural integrity of the othermicroseparator components. With reference to FIGS. 18A and 18B, forexample, the adsorbent array 700 can be released by disengaging thesecond surface 702 of the adsorbent array 700 from the first surface 821of the composite separator block 800.

Significantly, once the array 700 is released and removed from theplurality of microseparators, a different adsorbent array 700′ can besupplied to the microseparators. It may be desirable, in conjunctiontherewith, to provide a new releasable seal 300 between the adjacentsurfaces of the array 700 and the separator block 800.

Integrated Material Evaluation System

As noted, the chemical processing microsystem described in substantialdetail herein can be, and is preferably, integrated into a materialevaluation system for effectively and efficiently identifying newmaterials such as catalysts. Particular reference is made to FIG. 1B,FIG. 1C and FIGS. 18A and 18B, as well as the discussion provided inconnection therewith.

Process Characterization and/or Optimization

Chemical conversion is inherently process-intensive. As such, advancesin process knowledge, and improvements in process performance (e.g.,selectivity, yield) can be of significant commercial value. Thecombinatorial chemistry approach, and particularly, the devices andsystems disclosed herein, can be advantageously applied to processcharacterization and/or optimization research.

According to one approach for optimizing a chemical process, theparticular process of interest is effected in a multi-parallel fashionwhile varying only a limited number (e.g., one, two or three) of processconditions during each experiment. More specifically, one or morereactants are simultaneously supplied to each of four or moremicroreactors, a first set of reaction conditions is controlled to besubstantially identical in each of the four or more microreactors, asecond set of reaction conditions is controlled to be varied between twoor more of the microreactors, the first and second set of reactionconditions are controlled, collectively, to effect the chemical reactionof interest, a reactor effluent is discharged from each of the four ormore microreactors, and the effect of varying the second set of reactionconditions is evaluated. To optimize a particular chemical reaction, forexample, the same reaction can be effected simultaneously in two or moremicroreactors under reaction conditions that are substantially identicalin each microreactor, except as to the controlled variation of,independently or collectively, temperature, pressure, residence time,relative amount of reactants, relative amounts of catalyst, etc.Particular research strategies for a given process can be devised bypersons of skill in the art.

As such, the chemical processing microsystem of the present inventioncan be readily employed to conduct such parallel process research.Specifically, a plurality of microreactors can be configured to havesubstantially identical process conditions, except as to the controlledvariation in certain selected variables. As noted above, for example,and with reference to FIG. 8 and/or FIG. 18A, the temperature in each ofthe plurality of microreactors 600 can be varied between groups ofmicroreactors or between each of the microreactors 600 by providing atemperature gradient across the material-containing array 100, or byproviding spatially addressable independent heating elements toindividually control the temperature of each microreactor (or eachcandidate material). The pressure can be varied for a group ofmicroreactors or for each individual microreactor by using activepressure-control elements (e.g., individual valves for a group ofmicroreactors or for each microreactor) or passive pressure-controlelements (e.g., varying the conductance of the distribution channelserving a group of microreactors or serving each microreactor).Residence time can also be varied for a group of microreactors or foreach of the microreactors, for example, by designing each of theplurality of microreactors 600 included in the chemical processingmicrosystem 10 to have a different volume. Alternatively, variable flowcould be achieved to each microreactor. Catalyst amounts and/or surfaceareas can be readily varied by design, using fabrication methodologiesknown in the art. Moreover, catalyst structure can also be varied usingvarious material-deposition approaches.

Small Quantity Production

Many chemicals can be synthesized only, or more efficiently, byprocesses which are inherently hazardous, and/or can be hazardous orunstable to ship and/or store. As to such chemicals, the localized,small volume production thereof can be advantageously effected in themicroreactors and Microsystems of the present invention.

According to one approach for the production of small quantities of aparticular chemical of interest, one or more equivalent reactions can beeffected in each of a plurality of microreactors as described above,with or without the presence of a catalyst. The reaction products can beseparated, as described, and/or collected. The conversion and yield canvary substantially depending on the chemical be produced and themechanism employed. A mixture of products can also be established byvarying the reaction in each of the microreactors and then combining thereaction effluents or the collected reaction products.

The following examples illustrate the principles and advantages of theinvention.

EXAMPLES Example 1 Manufacture of Microreactor/Microseparator

A chemical processing microsystem, substantially as shown and describedin connection with FIGS. 18A and 18B, was manufactured as follows. Themicrosystem can be used, for example, to identify potentialheterogeneous catalysts for the direct amination of benzene to aniline.

Reactor Block Array

A first silicon/glass laminae substructure comprising 256 reactor blockwells, a fluid supply manifold/flow restrictor substantially as shownand described in connection with FIG. 7B, and a reactor effluent channelfor fluid communication with an effluent manifold was formed. Thelaminae substructure was fabricated from one 4″ diameter double polishedp-type Si(001) wafer (International Wafer Service) and one Pyrex 7740glass wafer (Corning) using standard microprocessing technology.

Fluid distribution components (supply manifold and reactor effluentchannels) were formed in the silicon wafer. Briefly, the silicon waferwas coated with 5000 Å low-stress Si₃N₄ in a silane/ammonia CVD tubereactor. 1 μm Shipley 1813 photoresist was spun onto both sides of thenitride-coated wafer and soft-baked at 90° C. for 15 minutes. One sideof this wafer was photolithographically exposed using a mask aligner(Electronic Visions) and subsequently developed using Shipley MF-319photoresist developer to pattern the channel structure into thephotoresist. Following development the wafer was hard-baked at 120° C.for 15 minutes. The silicon nitride was completely removed from theexposed areas in the photoresist using a SF₆+CF₃Br plasma in acapacitive plasma etcher (Drytek). All photoresist was then removed in a120° C. 2:1 solution of H₂SO₄:H₂O₂. The remaining silicon nitride wasused as an etch mask for etching the channels. A 22.5% KOH solution at80° C. was used to etch the channels. The etch rate was measured to be˜0.8 μm/min and the etch was timed to control the channel depth. Afterthe supply-manifold channels were etched, an array oftwo-hundred-fifty-six apertures (120 μm diameter) were created normal tothe silicon wafer surface using a YAG laser (CCT Laser Processing) foruse as the microreactor effluent channel. Finally, the silicon nitridewas removed in a solution of phosphoric acid at 150° C.

An array of two-hundred-fifty-six apertures (1 mm diameter) were createdin the Pyrex glass wafer using ultrasonic drilling for use as thereactor-volume-controlling portion of the reactor block wells.

The silicon wafer and glass wafer were then manually aligned withrespect to each other in an anodic bonding chuck (Electronic Visions),such that the array of apertures on the glass wafer were concentric withthe array of apertures on the silicon wafer. The silicon and glasswafers were then anodically bonded at 305° C. at 1000 Volts for 20minutes which produced a total charge displacement of around 2 Coulombsfor the wafer pair, thereby forming the laminae substructure having anarray of reactor blocks.

Catalyst Array

A catalyst array was created by sol-gel protocols using a 3″×3″ squareglass or quartz substrate (Chemglass) having an array oftwo-hundred-fifty-six wells arranged to correspond to the arrangement ofreactor blocks on the silicon/glass laminae substructure. The candidatematerials were candidate catalysts to be screened for their capabilityto catalyze the direct amination of benzene to aniline. The specificmethodology employed for forming the catalyst array is described incopending U.S. patent application Ser. No. 09/156,827, filed Jan. 18,1998 by Giaquinta et al.

Separator Block Array

A second silicon/glass laminae substructure comprising 256 separatorblock wells, a fluid discharge manifold such as shown and described inconnection with FIG. 14, and a microseparator inlet channel for fluidcommunication to the microseparator was formed. The laminae substructurewas fabricated from one 4″ diameter double polished p-type Si(001)wafers (International Wafer Service) and one Pyrex 7740 glass wafer(Corning) substantially as described above for manufacture of thereactor block array, except that the photoresist patterns were alteredsuch that the fluid-discharge manifold had a uniform width over each ofthe effluent paths (i.e., was not flow-restricting—substantially asdescribed in connection with FIG. 14).

Adsorbent Array

An asorbent array substrate was created in a third silicon/glass laminaesubstructure formed from a 4″ diameter silicon wafer and a 4″ diameterPyrex 7740 glass wafer having a thickness of about 0.5 mm. The glasswafer was ultrasonically drilled s with an array oftwo-hundred-fifty-six apertures (l mm diameter) arranged to correspondto the apertures formed in the separator blocks of the microseparators.The silicon and glass wafers were registrated with respect to each otheron the anodic bonding chuck and anodically bonded at 305° C. at 1000Volts for 20 minutes to form an array of two-hundred-fifty-sixcylindrical wells 1 mm in diameter and 0.5 mm deep.

An adsorbent suitable for detecting aniline was then deposited into eachof the wells of the adsorbent array substrate to form the adsorbentarray. The adsorbent was Adsorbosil-Plus-1 (Alltech), a silica gel withan inorganic binder (calcium sulfate). The as-purchased adsorbent wasmixed with water to form a slurry. An indicating dye for aniline wasincorporated into the slurry to assure uniform distribution of theindicator. The slurry was then trawled into the wells in theadsorbent-substrate laminae substructure using a razor blade. Extraslurry was removed from the wafer surface with the razor blade and thearray was allowed to dry at room temperature for one hour, and thenheated to 100° C. for one additional hour.

Temperature-Control Block

A 4″ diameter machinable ceramic insulating block (MACOR) having a totalthickness of about 2″ was employed as a temperature control blockbetween the microreactors and the microseparators. An array oftwo-hundred-fifty-six apertures (1 mm diameter) were formed in theinsulating block to operate as connecting channels—to provide fluidcommunication between each of the microreactor effluent (discharge)channels and each of the microseparator inlet channels. In otherembodiments, the insulating block was formed by combining several quartzblocks (0.5 inch). The connecting channels were formed therein by laserdrilling (diameters ranging from about 0.15 mm to about 0.5 mm).

Releasable Seals

Releasable seals were prepared from quartz paper sheets (Whatman) bymechanically punching an array of two-hundred-fifty-six aperturestherein with an array of pins. The aperatures were arranged tocorrespond to the array of microreactor blocks and the array ofmicroseparator blocks.

Chemical Processing Microsystem

The chemical processing microsystem was then formed from thesubcomponents in a housing substantially as shown and described inconnection with FIG. 18B. Briefly, the reactor block array and thecandidate material array were releasably integrated with each other toform an array of microreactors by aligning the array of candidatematerials with the array of reactor blocks with a releasable sealsituated therebetween. Similarly, the separator block array and theadsorbent array were releasably integrated with each other to form anarray of microseparators by aligning the adsorbent array with the arrayof separator blocks with a releasable seal situated therebetween. Thetemperature-control block was then situated between the array ofmicroreactors and the array of microseparators with the interconnectingchannels of the temperature-control block aligned to provide fluidcommunication therebetween and with releasable seals situated betweenthe temperature-control block and each of the microreactor array and themicroseparator array. The compressive fasteners of the housing were thenused to engage each the laminae to form the chemical processing microsystem.

Example 2 Operation of Parallel Microreactor/Microseparator

Catalyst Synthesis

Catalysts were formed using various methods known in the art and/ordescribed herein (See, especially, the examples in above-referenced,co-pending patent application U.S. Ser. No. commonly-owned co-pendingU.S. patent application Ser. No. ______, filed Mar. 1, 2000 by Lugmairet al. Chemical compositions of the catalyst libraries were generatedinteractively using LIBRARY STUDIO™ (Symyx Technologies, Inc.) librarydesign software, together with automated liquid handling equipment(Cavro Scientific Instruments, Inc.) under software control ofIMPRESSIONIST™ (Symyx Technologies, Inc). Briefly, catalysts were formedin 4 mm diameter wells on a 3″×3″ square glass or quartz wafer. Forimpregnation synthesis, slurried catalyst carriers were arrayed into thewells with a liquid handling robot. The slurries were dried andprefabricated support wafers were stored until needed for catalystlibrary synthesis. The catalyst impregnation was effected by incipientwetness technique. A synthesis robot generated an array of mixedmetal-salt precursor solutions in a microtiterplate. From thismicrotiterplate small volumes of liquid were transferred from each wellto a corresponding support. The volume of catalyst support and its poresize determined the volume transferred. After all desired supports havebeen impregnated, the wafer was dried at 120° C. for 1 hour and then themetal counter-ions were removed and metal oxides were formed by heatingto 350° C. for 3 hours in air. The impregnation, drying, calciningprocess was repeated multiple times to increase the catalyst loading inthe support. After synthesis was complete, the wafers were partiallyreduced, to form the desired catalyst. This processing was done in a 4″quartz tube furnace with wafers lying flat on a quartz slide.

Microreactor/Microseparator Operation

The reactant feed was a combination of gases and liquids. The gases weremetered using Unit 1661 MFC's in a z-block configuration. The liquidswere pumped with Gilson 361 HPLC pumps. The rates of gas and liquidflows were adjusted to achieve a residence time of 0.5 seconds. Aswitching valve allowed the reactor be either purged with nitrogen, orto be under flow from the reactant stream. Initially the microreactorwas in the purge mode and a catalyst wafer was loaded onto the heatedchuck and then pneumatically brought into contact with the inletdistribution manifold in the reactant block. On the opposite side of thereactor assembly, a commercial thin-layer chromatography plate cut to3″×3″ was placed in contact with the outlet (discharge) manifold of themicroseparator block. The cooling chuck was pneumatically brought downagainst the TLC plate and sealed the reactor assembly to the catalystwafer and the TLC plate. The system was allowed to thermally equilibratefor 5 minutes and then the gas stream was switched from nitrogen to thereactant feed stream. The reaction was run for fifteen minutes, duringwhich time reaction products were adsorbed (“trapped”) on the detectionplate, after which the feed stream was switched back to nitrogen.

The cold chuck was opened and the TLC plate was removed from themicroprocessing system. After removing the TLC plate, two or morecalibration spots were deposited onto the edge of the TLC plate with asyringe, typically, one with 20 ng of analyte and one with 200 ng ofanalyte. The TLC plate was placed into the spray station and the spraystation uniformly sprays the TLC plate with 5 ml of a fluorescaminesolution. The plate was removed from the spray station and placed intothe imaging station and allowed to develop for 2 minutes, after which a1024×1024 pixel image was taken with a CCD camera. The fluorescenceimage can be directly related to the analyte mass using the intensity ofthe calibration spots. The fluorescence is not a linear function ofanalyte concentration, so a calibration curve was measuredexperimentally (FIG. 20A). The microprocessing system was operatedeither in the low-mass linear portion of the fluorescence detectionsystem, or in some cases, the calibration curve was used to normalizethe data.

In one experiment, to measure the effect of the varying the catalystloading in the reactors, different wells were filled with a commercialbulk catalyst diluted with varying amounts of inert material. Each wellcontained a fixed amount of material, of which the catalyst fractionvaried from 10% to 100% catalyst, by weight, relative to total weight ofmaterial. Parallel reactions were effected as described above.Integrated intensities were measured and the variation between multiplewells of the same concentration was also measured (FIG. 20B). Somevariation within individual samples was observed (shown by error bars onFIG. 20B), primarily due to variations in the catalyst loadingattributable to manual loading procedures. Nonetheless, these data showthat final measured signal varied linearly with catalyst loading in thereactor, as expected.

In another set of experiments, it was verified that each microreactorwas independent of neighboring microreactors, by measuring cross-talkbetween channels. Catalysts were loaded into 14 different, spatiallyseparated wells on a 16×16 array of 256 wells formed in thematerial-containing laminate. The remaining wells contained no catalyst.After running the experimental protocol above, the plate was sprayedwith the dye, developed and imaged. FIG. 20C demonstrates that there isno appreciable cross-talk between channels, and that the active channelsare all of similar intensity—independent of their location on the wafer.These data, therefore, confirm the uniform distribution of reactantsbetween microreactors and the similar conditions in each microreactor.Additional tests were made with the same catalyst in every well and thedistribution of integrated intensities was measured. The measuredintensities for each microreactor/microseparator varied less than 15%from the average intensity. The primary sources of error in thisexperiment were the non-uniformity in the spraying of the dye, and thenon-uniformity of the UV illumination field in the imaging station, bothof which errors can be reduced through further development ofpost-reaction processing steps.

A further set of experiments were performed to test the wafer-basedsynthesis and microreactor/microseparator screening system forcorrelation to a known catalytic system. Briefly, wafer basedmixed-metal oxide ternary libraries were run in the microreactor systemas described above, and similar bulk catalysts were run in a moretraditional reactor with gas chromatograph detection. The same trends inactivity were seen in the wafer-based libraries using theabove-described reactor.

Additional experiments explored the effect of different parametersduring the discovery of heterogeneous catalysts. FIG. 20D shows anexample of 18 noble metal—transition metal—metal oxide ternaries on asingle catalyst wafer. This wafer was screened for catalytic activityusing the chemical processing microsystem of the invention substantiallyas described above. As shown in FIG. 20D, several compositions havingcatalystic activity—indicated by high intensity of fluorescence (brightspots) were determined. Once promising composition were identified,other compositional parameters, including for example, variations indopants and supports, were investigated in further experiments. Figure Eshows the data resulting from screening libraries comprising varyingdopant concentrations across a set of 18 ternaries. The then-mostpromising compositions (noble metal, transition metal, dopants) wereselected and then used in a further evaluation directed to determiningthe most promising support material.

Specifically, catalyst compositions were screened with a variety ofmetal-oxide supports, as shown in FIG. 20F, with different pore sizesand compositions. The resulting data show that zirconia is a preferredsupport, and that titania may also be useful as a catalyst support.Silica and alumnia were shown to be less desirable as catalyst supportsfor the reaction of interest.

In light of the detailed description of the invention and the examplespresented above, it can be appreciated that the several objects of theinvention are achieved.

The explanations and illustrations presented herein are intended toacquaint others skilled in the art with the invention, its principles,and its practical application.

Those skilled in the art may adapt and apply the invention in itsnumerous forms, as may be best suited to the requirements of aparticular use. Accordingly, the specific embodiments of the presentinvention as set forth are not intended as being exhaustive or limitingof the invention.

1-185. (canceled)
 186. A chemical processing microsystem comprising aparallel flow microreactor for evaluating catalyzed reactions, theparallel microreactor comprising a microreactor structure comprisingfour or more microreactors formed in a plurality of adjacent laminae,each of the four or more microreactors comprising a surface defining areaction cavity for carrying out a chemical reaction of interest, aninlet port in fluid communication with the reaction cavity, and anoutlet port in fluid communication with the reaction cavity, a fluiddistribution system for simultaneously supplying one or more reactantsfrom one or more reactant sources to the inlet port of each of the fouror more microreactors through a microfluidic fluid-supply manifold, andfor simultaneously discharging a reactor effluent from the outlet portof each of the four or more microreactors to one or more effluent sinks,and a temperature control device effective for controlling thetemperature of the reaction cavity to be above 100° C. during thechemical reaction of interest, at least one of the plurality of laminaebeing adaptable for use as a material-containing laminate that forms aportion of the cavity-defining surface of the four or moremicroreactors, the material-containing laminate comprising a substratefor containing at least four catalyst materials arranged on thesubstrate such that they are individually resident in the reactioncavities of the four or more microreactors, the four or moremicroreactors being accessible for loading the material-containinglaminate prior to carrying out the chemical reaction of interest, andfor unloading the material-containing laminate after the chemicalreaction of interest.
 187. The microsystem of claim 186 furthercomprising a releasable seal between the material-containing laminateand one or more adjacent laminae in which the microreactors are formed.188. The microsystem of claim 187 wherein the releasable seal is agasket.
 189. The microsystem of claim 187 wherein the releasable seal isa graphite gasket.
 190. The microsystem of claims 186 wherein themicrofluidic fluid-supply manifold is formed in a plurality of adjacentlaminae.
 191. The microsystem of claim 186 wherein the microfluidicfluid-supply manifold is formed in a plurality of adjacent laminaecomprising at least one laminate separate from the plurality of adjacentlaminae in which the microreactors are formed.
 192. The microsystem ofclaim 186 wherein the microfluidic fluid-supply manifold comprises acommon port adaptable for fluid communication with one or more reactantsources, four or more terminal ports adapted for fluid delivery to thefour or more microreactors, and a distribution channel providing fluidcommunication between the common port and each of the four or moreterminal ports, the flow paths defined between the common port and eachmicroreactors having equal conductance.
 193. The microsystem of claim186 wherein the microfluidic fluid-supply manifold comprises a commonport adaptable for fluid communication with one or more reactantsources, four or more terminal ports adapted for fluid delivery to thefour or more microreactors, and a distribution channel providing fluidcommunication between the common port and each of the four or moreterminal ports, the distribution channels being adapted such that thepressure drop in each of the fluid distribution channels is larger thanthe pressure drop in its associated microreactor.
 194. The microsystemof claim 186 wherein the fluid distribution system discharges thereactor effluent from the outlet port of each of the four or moremicroreactors to one or more effluent sinks through a microfluidiceffluent-distribution manifold.
 195. The microsystem of claim 186wherein the fluid distribution system discharges the reactor effluentfrom the outlet port of each of the four or more microreactors to one ormore effluent sinks through a microfluidic effluent-distributionmanifold formed in a plurality of adjacent laminae.
 196. The microsystemof claim 186 wherein the microfluidic fluid-supply manifold isreleasably sealed with a component of the microreactor structure, suchthat the manifold can be modularly interchanged with anothermicrofluidic fluid distribution manifold.
 197. The microsystem of claim186 wherein the microsystem has an essential absence of active mixingelements.
 198. The microsystem of claim 186 wherein the reactor geometryis adapted so that the microreactors are diffusion-mixed microreactors.199. The microsystem of claim 186 wherein the reactor geometry and theinlet port geometry is adapted so that the microreactors arediffusion-mixed without substantial back-diffusion of reactants into areactant supply manifold of the fluid distribution system.
 200. Themicrosystem of claim 186 wherein the temperature control device iseffective for controlling the temperature of the reaction cavity to beabove about 200° C. during the chemical reaction of interest.
 201. Themicrosystem of claim 186 wherein the temperature control device iseffective for controlling the temperature of the reaction cavity duringthe chemical reaction of interest to range from about 100° C. to about500° C.
 202. The microsystem of claim 186 wherein the temperaturecontrol device is effective for controlling the temperature of thereaction cavity during the chemical reaction of interest to range fromabout 100° C. to about 800° C.
 203. The microsystem of claim 186 whereinthe fluid distribution system is effective for supplying one or moregaseous reactants through the microfluidic fluid-supply manifold. 204.The microsystem of claim 186 wherein the fluid distribution system iseffective for supplying one or more gaseous reactants through themicrofluidic fluid-supply manifold, and the temperature control deviceis effective for controlling the temperature of the reaction cavity tobe above about 200° C. during the chemical reaction of interest. 205.The microsystem of claim 186 wherein the chemical processing microsystemfurther comprises four or more inorganic candidate catalyst materialsindividually resident in each of the four or more microreactors. 206.The microsystem of claim 186 wherein the reaction cavities of the fouror more microreactors are isolated from each other.
 207. The microsystemof claim 186 wherein the outlet port from a first reaction cavity is influid communication with an inlet port of a second reaction cavity. 208.The microsystem of claim 186 wherein the fluid distribution systemdischarges the reactor effluent from the outlet port of each of the fouror more microreactors to one or more effluent sinks through amicrofluidic effluent-distribution manifold, the microfluidicfluid-supply manifold and the microfluidic effluent-distributionmanifold being formed in the same common plurality of laminae.
 209. Themicrosystem of claim 186 wherein the fluid distribution systemdischarges the reactor effluent from the outlet port of each of the fouror more microreactors through a microfluidic effluent-distributionmanifold, the reactor effluent streams being discharged from the four ormore reactor outlet ports as four or more independent streams.
 210. Themicrosystem of claim 186 wherein the fluid distribution systemdischarges the reactor effluent from the outlet port of each of the fouror more microreactors to one or more effluent sinks through amicrofluidic effluent-distribution manifold, the microfluidicfluid-supply manifold and the microfluidic effluent-distributionmanifold being formed in the same common plurality of laminae, thereactor effluent streams being discharged from the four or more reactoroutlet ports as four or more independent analytical sample streams. 211.The microsystem of claim 186 further comprising four or more paralleldetectors to simultaneously analyze reaction products or unreactedreactants of each of the four or more effluent streams.
 212. Themicrosystem of claim 186 further comprising four or more paralleldetectors to simultaneously analyze reaction products or unreactedreactants of each of the four or more effluent streams, wherein thefluid distribution system discharges the reactor effluent from theoutlet port of each of the four or more microreactors to one or moreeffluent sinks through a microfluidic effluent-distribution manifold,the microfluidic fluid-supply manifold and the microfluidiceffluent-distribution manifold being formed in the same common pluralityof laminae, the reactor effluent streams being discharged from the fouror more reactor outlet ports as four or more independent analyticalsample streams to the four or more parallel detectors.
 213. A chemicalprocessing microsystem comprising a parallel flow microreactor forevaluating catalyzed reactions, the parallel microreactor comprising amicroreactor structure comprising four or more microreactors, each ofthe four or more microreactors comprising a surface defining a reactioncavity for carrying out a chemical reaction of interest, an inlet portin fluid communication with the reaction cavity, and an outlet port influid communication with the reaction cavity, a microfluidic fluiddistribution system for simultaneously supplying one or more reactantsfrom one or more reactant sources to the inlet port of each of the fouror more microreactors through a microfluidic fluid-supply manifold, andfor simultaneously discharging a reactor effluent from the outlet portof each of the four or more microreactors through a microfluidiceffluent-distribution manifold, the microfluidic fluid-supply manifoldand the microfluidic effluent-distribution manifold being formed in thesame common plurality of laminae, the reactor effluent streams beingdischarged from the four or more reactor outlet ports as four or moreindependent effluent streams, four or more parallel detectors inrespective fluid communication with the four or more independenteffluent streams, for simultaneously analyzing reaction products orunreacted reactants in each of the four or more independent effluentstreams, and a temperature control device effective for controlling thetemperature of the reaction cavity to be above 100° C. during thechemical reaction of interest.
 214. The microsystem of claim 213 whereinthe four or more microreactors are formed in a plurality of adjacentlaminae, at least one of the plurality of laminae being adaptable foruse as a material-containing laminate that forms a portion of thecavity-defining surface of the four or more microreactors, thematerial-containing laminate comprising a substrate for containing atleast four catalyst materials arranged on the substrate such that theyare individually resident in the reaction cavities of the four or moremicroreactors, the four or more microreactors being accessible forloading the material-containing laminate prior to carrying out thechemical reaction of interest, and for unloading the material-containinglaminate after the chemical reaction of interest.
 215. The microsystemof claim 213 wherein the temperature control device is effective forcontrolling the temperature of the reaction cavity to be above about200° C. during the chemical reaction of interest.
 216. The microsystemof claim 213 wherein the temperature control device is effective forcontrolling the temperature of the reaction cavity during the chemicalreaction of interest to range from about 100° C. to about 500° C. 217.The microsystem of claim 213 wherein the temperature control device iseffective for controlling the temperature of the reaction cavity duringthe chemical reaction of interest to range from about 100° C. to about800° C.
 218. The microsystem of claim 213 wherein the fluid distributionsystem is effective for supplying one or more gaseous reactants throughthe microfluidic fluid-supply manifold.
 219. The microsystem of claim213 wherein the fluid distribution system is effective for supplying oneor more gaseous reactants through the microfluidic fluid-supplymanifold, and the temperature control device is effective forcontrolling the temperature of the reaction cavity to be above about200° C. during the chemical reaction of interest.
 220. The microsystemof claim 213 wherein the reaction cavities of the four or moremicroreactors are isolated from each other.